Method for determining sodium clearance of dialyzer

ABSTRACT

A method is described for determining the sodium clearance of a dialyzer. Dialysate containing sodium ions is circulated through the dialysate side of the dialyzer. Water is continuously circulated through the blood side of the dialyzer, the water being single passed through the blood side of the dialyzer. Measurements of the conductivity of the dialysate are made prior to the dialysate entering the dialyzer, and measurements of the conductivity of the dialysate are made after the dialysate has passed through the dialyzer. The clearance of the sodium ions by the dialyzer is calculated from the measurements of conductivity. The measurements of conductivity of the dialysate after passing through the dialyzer becomes substantially constant as the dialysate and water are circulated through the dialyzer. The sodium clearance corresponds to urea clearance of the dialyzer, since the two molecules are approximately the same size.

This application is a continuation of application Ser. No. 08/559,925,filed Feb. 27, 1996, now abandoned, which is a divisional of applicationSer. No. 08/388,275, filed Feb. 13, 1995, now U.S. Pat. No. 5,591,344.

A portion of the disclosure of this parent document contains mattersubject to copyright protection. The copyright owner has no objection tothe facsimile reproduction by anyone of the patent disclosure, as itappears in the Parent and Trademark Office files and records, butotherwise trains all copyright rights whatsoever.

FIELD OF THE INVENTION

The invention relates to dialysis machines, their constituent componentsand subsystems, and their methods of operation. The dialysis machine ofthe present invention is particularly suitable for use outside of aconventional dialysis clinic, e.g., in a home, self-care clinic, ornursing home environment.

BACKGROUND OF THE INVENTION

Dialysis, including hemodialysis and peritoneal dialysis, is a treatmentmode for patients that suffer from inadequate kidney function. Inhemodialysis, blood is pumped from the patient's body through anextracorporeal artificial kidney (dialyzer) circuit, where blood-bornetoxins and excess water are filtered out of the blood through asemipermeable membrane into an electrolyte (dialysate) medium. Acommonly used form of dialyzer comprises a large number of semipermeablehollow fiber membraned, which greatly increase the surface areaavailable for dialysis to facilitate diffusion and convection across themembranes.

Existing dialysis systems typically consist of two parts; one comprisingan extracorporeal blood flow circuit and the other comprising adialysate circuit or flow path. Typically, the entire blood flow circuitis disposable and comprises: 1) an arterial and venous fistula needle,2) an arterial (inflow) and venous (outflow) tubing set, 3) a dialyzer,4) physiologic priming solution (saline) with infusion set, and 5) ananticoagulant, such as heparin or sodium titrate with infusion set. Thearterial needle accesses blood from the patient's blood access site andis connected to the arterial blood tubing set, which conveys blood tothe dialyzer.

The arterial line typically comprises: a pumping segment with interfacesm a rotary or peristaltic blood pump on the hemodialysis machine,pressure monitoring chambers including tubing which interfaces topressure transducers on the machine to monitor the pressure pre-pumpand/or post pump, inlet ports for saline and anticoagulant, and one ormore injection sites for drawing blood or injecting drugs.

The dialyzer itself typically comprises a case which encloses a bundleof hollow fibers having a semi-permeable membrane. The blood iscirculated on the inside of the hollow fibers while dialysis solution iscirculated on the outside, so that the two never come into directcontact. Toxins diffuse out of the blood and into the dialysis solutionowing to the concentration gradient. Excess water in the patient's bloodenters the dialysate as a result of a pressure gradient. The membrane ismade from cellulosic derivatives or synthetic polymers.

The venous line and needle carry the newly dialyzed blood away from thedialyzer and back into the patient's circulatory system. The venous setis comprised of a pressure monitoring chamber with tubing leading toanother pressure transducer in the machine, injection sites, and asegment of tubing which interfaces to an air detection assembly in themachine in order to prevent air emboli from passing to the patient.

Dialysis solution is typically prepared continuously on-line inpresent-day machines by combining water which has first been purified bya separate water treatment system and liquid concentrates ofelectrolytes. Over the past decade the dialysate concentrates haveevolved from a single formulation which contained acetate as thephysiologic buffering agent for the correction of circulatory acidosis,to two containers where bicarbonate replaces acetate as the bufferingagent. Two proportioning pumps are required, the tint to mix thebicarbonate concentrate with water and the second to proportion thismixture with the concentrated electrolytes to achieve the final,physiologically compatible solution.

Most contemporary hemodialysis machines continuously monitor thepressure at the blood outlet side of the dialyzer by way of the pressuretransducers connected to the blood sets and also in the dialysatecircuit. Microprocessors calculate an estimated transmembrane pressure(TMP) which correlates to the amount of water transmission through themembrane. These machines may also have means of measuring the amount ofdialysis solution entering and leaving the dialyzer, which allows thecalculation of net water removal by ultrafiltration from the patient. Byelectronically comparing the amount of water entering or leaving theblood with the transmembrane pressure, the system is able to controlactively the water removed from the patient to a desired targetpreviously programmed into the system. When low-water-transmissioncellulosic membranes are employed negative pressure must be generated onthe dialysate side of the membrane by the machine in order to accomplishsufficient water removal. Because suction may be applied to thedialysate as it transits the dialyzer, it must first be placed under agreater vacuum in a degassing chamber so that air bubbles are notgenerated within the dialyzer that would cause errors in the calculationof ultrafiltration by the sensors and also reduce the efficiency of thedialyzer. On the other hand, when high-water-transmission, syntheticmembranes are used, it is frequently necessary to apply positivepressure on the dialysate side to control the otherwise excessive rateof ultrafiltration.

The majority of dialyzers are reused in the United States. The trendworldwide is towards reusing dialyzers. Then are numerous procedures forreusing dialyzers both manually and automatically. In centers, specialmachines for simultaneous multiple dialyzer reprocessing an used.

These procedures must be conducted in a biohazard environment since thenis always the potential for exposure to human blood, and hepatitis andAIDS are relatively prevalent in the dialysis population. Also, the OSHAand EPA stipulate various working environment regulations owing to thehazardous sterilizants and cleaning agents used.

Reprocessing of dialyzers and lines may be performed on the dialysismachine. The Boag patent, U.S. Pat. No. 4,695,385, discloses a cleaningapparatus for dialyzer and lines. The device is permanently orsemipermanently connected into the dialysis machine system.

Finally, the dialysis machine fluid circuits must be periodicallycleaned and disinfected. There are two reasons for this. The firstrelates to the fact that the dialysate has historically not beensterile. From the very beginning of dialysis as a therapy, the dialyzermembrane has been relied upon to be a sterile barrier between dialysateand blood. This is certainly true for whole bacteria, but concern hasbeen growing over the past several years that with the use of syntheticmembranes and their more porous structure, endotoxins, or componentsthereof, may by permeating these membranes and activating inflammatoryprocess within the patients. When dialysate containing bicarbonate isused, calcium carbonate inevitably precipitates and accumulates on theplumbing and must be dissolved with an acidic solution.

Historically, many artificial kidneys have utilized a proportioningsystem for producing dialysis solution and delivering it into ahemodialyzer. In the early years of hemodialysis only a so-called tankor hatch system was used. The machine was provided with a large tankwhere purified water was premixed with dry chemicals to make dialysissolution, which was warmed and recirculated through the dialyzerdialysate path. Bicarbonate was used as a buffer; CO₂ was bubbledthrough the solution, or tactic acid was added to the solution toprevent calcium/magnesium carbonate precipitation. With inefficientdialyzers, a dialysis time of 12 hours or more was used. Warm dialysatewas an excellent culture medium for bacterial growth. Long dialysistreatment time magnified the problem. To overcome this problem aproportioning system was designed whereby the solution was beingprepared ex tempore from purified water and concentrate. The concentratecontained acetate as the physiologic buffering agent because bicarbonatetended to precipitate with calcium and magnesium if present in the sameconcentrate.

As of the mid-1990's there are approximately 180,000 patients ondialysis in the United States, almost 500,000 worldwide. Most of themdialyze in hemodialysis centers and approximately 17% are on homeperitoneal dialysis with less than 3% on home hemodialysis. Typically,in-center hemodialysis is performed three times per week for between twoand four hours. The more physiologically desirable four times per weekdialysis sessions are used only with patients with severe intolerance tothree times weekly dialysis, generally due to cardiovascularinstability. Home hemodialysis is also typically performed three timesweekly.

Three dialysis sessions per week is considered a standard schedule inthe majority of dialysis centers, yet there is considerable scientificevidence that more frequent dialysis for shorter periods of time is morebeneficial. Whereas the normal human kidneys function continuously toproduce gradual changes in total body fluid volume and metabolic wastelevels, three times weekly dialysis schedules produce abnormalphysiological fluctuations which yield considerable stress on thepatient's systems.

The mount of time consumed travelling to and from the center, and thedialysis procedure itself, is mostly tolerable for the patients whoperform three sessions per week. Consequently, only those patients whoexperience unbeatable intolerance of body fluid volume fluctuations, andthe associated symptoms, agree to more frequent (four times weekly)dialysis sessions. For home dialysis patients, more frequent dialysisthan three times per week would mean more stress on the relatives whohelp with set-up and who monitor the patient and on the patient who doesmost of the work for set-up, tear-down, and cleaning. Accordingly, theuse of home hemodialysis on a frequent basis (four or more times perweek) has, at least heretofore, not been widely practiced.

Many patients have enormous difficulties achieving a "dry" body weightif they accumulate three, four, or more kilograms of fluid betweendialysis treatments. Some patients, especially those with heart disease,poorly tolerate even a two kilogram fluid weight gain; they are short ofbreath before dialysis, have muscle cramps and hypotension duringdialysis, and feel "washed out" and are extremely weak, needing severalhours to "equilibrate" and become functional. Serum concentration ofhighly toxic potassium frequently reaches dangerous levels (more thanseven mEq/L), particularly preceding the first dialysis after a longerinterval (weekend). To mention only a few others, calcium and pH are toolow before dialysis or too high afar dialysis in many patients.Empirically, in many hemodialysis units, these patients are placed on afour times weekly dialysis schedule.

Historically, artificial kidney systems were developed according to theassumption that the machine should be very sophisticated and automatedduring dialysis and less so for preparations and cleansing. Thisassumption was valid for long and infrequent dialysis sessions wherecompared to the total dialysis time the time for setup and cleansing ofthe machines was relatively short.

More efficient dialyzers were eventually designed, and time of a singledialysis session gradually decreased to 8, 6, 5, 4, 3, and even 2 hours.With very efficient dialyzers, acetate was delivered to the patient inexcess of the body ability to metabolize it, which caused cardiovascularinstability. An answer to this problem was to return to bicarbonate as abuffer but within an overall design of proportioning system. Because ofchemical incompatibility of bicarbonate with calcium and magnesium, twoproportioning pumps are required, the first to mix the bicarbonateconcentrate with water and the second to proportion this mixture withthe concentrated electrolytes to achieve the final, chemicallycompatible solution. However, a short daily dialysis session of 1-3hours often a possibility of abandoning the proportioning system.

If short daily hemodialysis is done in a dialysis clinic, the traveltime, inconvenience and expense incurred by the patient increasesdramatically. If such a practice is adopted by a large number of thecenter's patients, the staff at the treatment center is also burdened.Additionally, the dialysis facility's capacity for performing thisnumber of incremental treatments would have to be increased, requiringcapital expansion. Consequently, the patient's home is a desirablelocation for this treatment modality.

U.S. Pat. No. 5,336,165 to Twardowski describes techniques forovercoming many of the problems associated with conventional dialysisdevices. This patent describes a hemodialysis system which has abuilt-in water treatment system; automatic formulation of batch dialysissolution; automated reuse; automated set-up; automated cleaning anddisinfection of blood and dialysate circuits; and reduction in storagespace by utilizing dry and concentrated chemical reagents. This systemis suitable for home dialysis.

The failure of home hemodialysis to achieve the widespread popularity isdue partly to the failure in the art to produce a user-friendly,efficient, and affordable home hemodialysis system that relieves thepatient and the patient's family from time-consuming and tediouspre-treatment and post-treatment set-up and teardown of the homehemodialysis equipment. The present inventive machine remedies thissituation, offering patients a hemodialysis system particularly suitablefor short daily hemodialysis in the home environment.

The present invention relates to a modular hemodialysis machineespecially suitable for use in the home environment that provides for acost-effective, transportable, simple and highly reliable homehemodialysis system that automates substantially the entire process andrequires a minimum of patient input and labor. By substantially reducingthe labor intensity and disposables cost associated with prior art homehemodialysis treatment equipment, the present invention is intended toopen up the availability of short daily hemodialysis in the homeenvironment to a larger pool of hemodialysis patients. These patients,by practicing the present invention, can avail themselves of thistreatment modality, which has proven to yield outstanding clinicalbenefits, without having the inconvenience of travel to remote treatmentcenters.

SUMMARY OF THE INVENTION

A method is provided for approximating the sodium clearance a dialyzer.The dialyzer has a membrane with a dialysate side and a blood side. Themethod comprises the steps of:

circulating dialysate containing sodium ions through the dialysate sideof the dialyzer;

continuously circulating water through the blood side of the dialyzer,the water being single passed through the blood side of the dialyzer;

measuring the conductivity of the dialysate prior to entering thedialyzer;

measuring the conductivity of the dialysate after the dialysate haspassed through the dialyzer; and

calculating the clearance of the sodium ions by the dialyzer from themeasurements of conductivity. The measurement of conductivity of thedialysate after passing through the dialyzer become substantiallyconstant as the dialysate and purified water are circulated through thedialyzer. The sodium clearance corresponds to the urea clearance of thedialyzer, since the two molecules are approximately the same size.

BRIEF DESCRIPTION OF THE DRAWINGS

In the following detailed description of the presently preferredembodiments of the invention, reference will be made to the accompanyingdrawings, wherein like numerals in the drawings refer to like elementsin the various views, and wherein:

FIG, 1 is a schematic block diagram of the overall system, showing therelationship between a water pretreatment module, a modular homedialysis machine and the patient;

FIG. 2 is a detailed schematic diagram of the water pretreatment moduleof FIG. 1;

FIG. 3A is a perspective view of the water filtration unit 40 of FIG. 2,showing the path of water through the water filtration unit;

FIG. 3B is a perspective view of the secondary water filtration unit 84of the water treatment module 24, showing the flow of water through onehalf of the unit;

FIG. 4A is a cross-sectional view of the pressure relief valve 78 withintegral sample removal port of FIG. 2;

FIG. 4B is a detailed view of the upper portion of the pressure reliefvalve 78 of FIG. 4A during removal of a sample from the valve;

FIG. 4C is a perspective view of an alternative construction for thecentral member 146 of FIG. 4A;

FIG. 4D is a perspective view of the insert of FIG. 4A;

FIG. 5 is a detailed schematic diagram of the water treatment module 24of FIG. 1;

FIG. 6 is a detailed schematic diagram of the hydraulic or dialysatepreparation module 26 of FIG. 1;

FIGS. 7A-7C are several views of the chemical loading platform 250 ofFIG. 6; FIG. 7D is a sectional view of the loading platform of FIG. 7Aalong the lines 7D of FIG. 7B, showing the sprayer inserted within thehousing; FIG. 7E is an end view of the loading platform of FIG. 7A; FIG.7F is a horizontal cross sectional view of the loading platform of FIG.7A taken along the lines 7F of FIG. 7E;

FIGS. 8A-8C are several views of the chemical applicator system 260 ofFIG. 6;

FIG. 9A-9C are several views of the mounting member 354 of the chemicalapplicator 260 of FIGS. 8A-8C;

FIGS. 10A-10F are several views of the chemical bottle 270 of FIG. 6;

FIG. 11A is a plan view of the noninvasive conductivity cell 218 of FIG.6, FIG. 11B is a plan view of an alernative noninvasive conductivitycell 218;

FIG. 12 is a sectional view of the chemical applicator and bottle ofFIG. 6 during rinsing of the bottle;

FIG. 13 is a schematic diagram of the extracorporeal circuit module 28of FIG. 1;

FIG. 14A-14B are several views of the noninvasive pressure sensor 500 ofthe extracorporeal circuit module 28 of FIG. 13, FIG. 14C is a sectionalview of the diaphragm of FIG. 14A;

FIGS. 15A-15D are several views of a cassette-style debubbler for use inthe extracorporeal circuit module 28 of FIG. 13;

FIG. 16 is a block diagram of the user interface and control module 25of FIG. 1, showing its relationship to the various sensors andcomponents of the machine;

FIG. 17 is a flow diagram of the sequence of steps of the operation ofthe machine;

FIG. 18 is a flow diagram of the sequence of events during the disinfectstep of FIG. 17;

FIG. 19 is a flow diagram of the sequence of events during the preparedialysate step of FIG. 17;

FIG. 20 is a flow diagram of the sequence of events during the initiatedialysis step of FIG. 17;

FIG. 21 is a flow diagram of the sequence of events during the dialyzestep of FIG. 17, showing in particular the periodic backflush of thedialyzer 404 during dialysis;

FIG. 22 is a flow diagram of the sequence of events during the rinsebackstep of FIG. 17;

FIG. 23 is a flow diagram of the sequence of events during the clean andrinse step of FIG. 17;

FIG. 24A-24B are two views of a technique for securing silicone tubingsuch as that used in the present invention to a hardware component, suchas, for example, a pump or valve;

FIG. 25A is a schematic diagram of the blood leak detector 428 of FIG.13;

FIG. 25B is a diagram of the flow of signals in the blood leak detectorof FIG. 25A;

FIG. 26 is a diagram of conductivity as a function of time measured bythe conductivity sensors 218 and 426 during the clearance test 743 ofFIG. 19;

FIG. 27 is an elevational view of the extracorporeal circuit module 28of FIG. 13; with the arterial 432 and venous 492 blood tubes shown indashed lines connected to the disinfection manifold 494, as they wouldbe when the dialysis session has been completed; and

FIGS. 28-33C are tables of the state of the components of the machine 22of FIG. 1 during the modes of operation of the machine illustrated inFIGS. 18-23;

FIGS. 34-35B are tables of the state of the alarms of the machine 22 ofFIG. 1 during the modes of operation of the machine illustrated in FIGS.18-23;

FIG. 36 is a detailed perspective view of the disinfection manifold 494of FIG. 13;

FIGS. 37A-37C are several views of a male luer 550 of a tubingconnection terminal for use with the disinfection manifold of FIG. 36;

FIG. 37D is an illustration of a connection of an alternativeconstruction of a male luer from the embodiment of FIG. 37A onto afemale luer;

FIG. 38A is a perspective view of the male luer 550 of FIG. 37 shownprior to insertion of an outer piece 570 thereover, the male luer andouter pieces forming a unitary tubing connector;

FIGS. 38B-38C are several view of the outer piece 570 of FIG. 38A;

FIG. 38D is an elevational view and partially broken away of the robingconnector of FIG. 38A in an assembled condition;

FIGS. 38E-G are illustrations of alternative constructions of theconnector of FIG. 38A;

FIG. 39A-39C are several views of preferred design for the ports of thedisinfection manifold 494 of FIGS. 13 and 36;

FIG. 39D is a sectional view of the port of FIG. 39C with the tubingconnector of FIG. 38D installed therein;

FIG. 39E is a perspective view of the construction of FIG. 39D partiallybroken away;

FIGS. 40A-40E are several views of the knob 641 of the port 499 of FIG.39E;

FIG. 41 is an illustration of a hemofiltration with pre-dilutionembodiment of the invention;

FIG. 42 is an illustration of a hemofiltration with post-dilutionembodiment of the invention; and

FIG. 43 is an illustration of a hemodiafiltration with post-dilutionembodiment of the invention.

DETAILED DESCRIPTION AND BEST MODE OF PRACTICING THE INVENTION

Referring to FIG. 1, a preferred embodiment of the overall inventivemachine and system is shown in block diagram form. The modular dialysismachine 22 receives water from a water pretreatment module 20. Thepretreatment module 20 and modular dialysis machine 22 are showninstalled, for purposes of example and not limitation, in a patient'shome environment. The primary functions of the water pretreatment module20 are to provide preliminary treatment of water from a household watersupply, to provide treated water at a predetermined warmed temperatureand pressure to the dialysis machine 22, and to carry system drain andwaste water from the dialysis machine 22 to a household drain. Thedialysis machine 22 is a preferably a moveable unit, mounted on wheels,that houses three functionally discrete modules: a water treatmentmodule 24, a dialysate preparation or hydraulic module 26 and anextracorporeal circuit module 28. The patient in need of dialysis (notshown) is connected to the extracorporeal circuit module 28 inconventional fashion with two lines designated "arterial" and "venous".

The dialysis machine 22 further includes a patient interface and controlmodule 25 including a display and a touch screen (or other patient inputmeans, such as a keyboard) connected to one or more central processingunits. The interface and control module 25 exercises supervisory controlover the operation of the system, displays the current status of themachine, prompts the user to input commands and information, receivesdata from the various sensors and other passive components of thesystem, records the data in memory, controls the operation of the activecomponents of the machine (such as valves, pumps, heaters, etc.), alertsthe patient to abnormal or failure conditions in the machine with alarmsor other indicators, calculates parameters relating the hemodialysis,and performs additional tasks as discussed in detail below.Additionally, the interface and control module 25 may be provided withadditional hardware components to permit the machine 22 to send patientdialysis information to a central monitoring station electronically,such as by modem.

I. Water Pretreatment Module 20

Referring now to FIGS. 1 and 2, the water pretreatment module 20 isshown installed in a cabinet 32 under a sink 34 (FIG. 1). The waterpretreatment module 20 could also be a mobile unit, in which flexiblelines connect the module 20 to the household hot and cold water pipes.Referring in particular to FIG. 2, hot and cold water is tapped off ahousehold water system and fed to a temperature-controlled mixing valve36, where the water is mixed to maintain a constant temperature of 28 to30 degrees C in the output line 37. A suitable temperature-controlledmixing valve is available from Grohe, part no. 34 448. The warm water ispassed through a water pressure regulator 38 past a manually operatedvalve 39 to a replaceable integral water filtration and treatment unit40. A preferred pressure regulator 38 can be obtained from Norgren.

A preferred water treatment unit 40 is the ROPAK unit from Millipore,part no. MSPB00168. Referring to FIG. 3A, the water treatment unit 40has a unitary housing 47 containing four chambers 49A-49D. The waterenters the chamber 49A via water inlet 41A. Chamber 49A is loaded with aparticle filtration agent 42 that filters the water for particulatematter. After passing through the particulate 42, the water is passedthrough a second chamber 49B and a third chamber 49C loaded with acarbon filtration agent 44 which removes organic material and dissolvedgasses from the water. The water then passes into a fourth chamber 49Dcontaining a polyphosphate softening agent 43 and passes through thepolyphosphate water softening agent and out the outlet 45A.

Water is sent out of the water filtration unit 40 in line 46 and sent toa pressure relief valve 78 with an integral port for manual removal ofsamples of water to test for the presence of chlorine or chloramines inthe water in the line 46. An outlet 50 direct the flow of water from thewater pretreatment module 20 to a water inlet. 52 in the dialysismachine 22 via a flexible hog 54. The water pretreatment module 20 has adrain inlet 56 that receives waste water from the dialysis machine 22via flexible hose 58, and sends such waste water through a drain line62, past check valve CV3 to a household drain 60. It may be advisable toswitch input and output hoses 54, 58 periodically to avoid buildup ofany organic matter in the input hose 54, which might occur since thewater going to the machine normally contains no chlorine.

The provision of a temperature-controlled mixing valve 36 to mixhousehold hot and cold water offers numerous advantages. The watertemperature that is input into the dialysis machine 22 at inlet port 52is controlled and maintained at a constant temperature (ideally 28 to 30degrees C.). This decreases the power consumption of the machine 22,since the machine 22 heating load is minimized, as the machine 22 doesnot have to heat up cold water. Further, the temperature-controlledmixing valve 36 supplies water into the water treatment module 24 closeto the temperature at which the reverse osmosis filter 100 (FIG. 5)membrane is most efficient. This maximizes the throughput of water intothe machine 22, thereby reducing water consumption. It should be notedthat the temperature-controlled mixing valve 36 could be installed inthe inlet circuit of the water treatment module 24 in the event that awater pretreatment module 20 is not used, for whatever reason, with thebenefits still obtained.

The pressure regulator 38 further supplies water to the dialysis machine22 at a substantially constant pressure. A pressure relief valve 78 withintegral water sample removal port provides a means for permitting theremoval of water from the line 46 downstream of the water treatment unit40 and to thereby allow for testing of a water sample for the presenceof chlorine or chloramines in the water. The sample port allows a fluidsample to be taken from the fluid flow path (i.e., water in line 46)without contaminating the sample. The sample is taken with a syringe orother suitable implement.

The pressure relief valve 78 with integral sample removal port 138 isshown in a cross-section in FIG. 4A. The valve 78 consists of a standardadjustable pressure relief valve housing having an adjustment member 130which screws clockwise or counterclockwise relative to housing 133,thereby adjusting the force that the pressure relief spring 144 appliesto the plastic plunger 142 and elastomeric diaphragm 140. Theelastomeric diaphragm 140 provides a lower boundary to an upper chamber131. The relief valve housing member 132 has a fluid inlet tube 134 anda fluid outlet tube 136. An integral sample removal port 138 is providedat the base of the housing 132.

A cylindrical member 146 is placed within the principal fluid passagechamber 137 with the top rim 139 normally flush against the bottom ofthe diaphragm 140, thereby preventing entry of fluid over the rim andinto the cylindrical member 146 and out the sample removal port 138under normal pressure conditions in the unit 78. Preferably, thecylindrical member is integrally formed with the housing 132 of thepressure relief valve. In the alternative construction of FIG. 4C, thecylindrical member 146 is shown as a separate piece and is threaded ontothe base of the housing 132 just above the sample removal port 138.

A cylindrical plastic 148 with a lower tip 152 and an upper surface 154is placed within the cylindrical member 146. The insert 148 is shownisolated in perspective view in FIG. 4D. The purpose of the insert 148is to transmit forces from the tip of a syringe 135 inserted into thesample removal port against the base of the diaphragm 140 to lift thediaphragm above the rim 139 of the cylindrical member 146, therebyallowing fluid to escape over the rim 139 down into the sample removalport 138.

FIG. 4B is a detailed view of the upper portion of the chamber 137 whenthe insert 148 is pushed by the rip of the syringe 135 into an upperposition. Referring to FIGS. 4A and 4B, when the user wishes to remove asample, the user inserts the tip 150 of a syringe 135 into the sampleremoval port 138. The rip 150 of the syringe 135 pushes against thebottom tip 152 of the cylindrical insert 148, causing the upper portion154 to push the diaphragm 140 upwards (FIG. 4B). Fluid in the chamber137 now flows over the rim 139 into the interior region of thecylindrical member 146 (see arrows) and down into the region 156surrounding the insert 148 and into the sample removal port 138, fromwhere it is pulled into the syringe 135.

Chlorine and chloramines have a high level of toxicity to hemodialysispatients, hence their removal from the water used in the dialysate isimperative. The carbon filter agent 44 of water filtration unit 40removes such substances from the water line, but in the event that thecarbon filter agent 44 has exhausted its capacity to remove chloraminesor chlorine, the user will need to replace the water filtration unit 40.After each use of the machine, the user inserts a syringe into thesample removal port, withdraws a sample of the water, and applies thesample to a chloramines or chlorine reagent test strip to see if a colorchange in test strip occurs, indicating that chlorine substances are inthe sample. A preferred source for the test strips is Serim ResearchCorporation, P.O. Box 4002, Elkhart, Ind. 46514-0002.

The presence of chlorine or chloramines in a household water supply isordinarily attributable to municipal water treatment efforts. If thecarbon filter agent 44 of the water pretreatment unit 40 is workingproperly, the chloramine level in line 46 is normally zero. However, ifthe carbon filter 44 is exhausted, the secondary carbon filter 88 inwater treatment module 24 (FIG. 5) removes the chloramines from thewater, insuring safety of the system. Ideally, the user checks forchloramines daily after each dialysis treatment, thereby insuring thatin the case that the primary chloramine filter agent (e.g., filter 44)is exhausted, the backup secondary carbon filter 88 does not also becomeexhausted.

Thus, the present invention provides a method for treating water usedfor the preparation of a dialysate solution in a dialysis machine,comprising the steps of passing water through a first filter (e.g.,carbon filter 44) having chlorine removal properties and pissingfiltered water into a line, removing water from the line andperiodically sampling the removed water for the presence of chlorine orchloramines, the presence of chlorine or chloramines indicating that thefiltration capacity for chlorine of the first filter is substantiallyexhausted, filtering the water downstream from the sample location in asecond filter (e.g., carbon filter 88) also having chlorine removalproperties, and replacing the first filter if chlorine or chloraminesdetected during the sampling step.

If the user does not use a water pretreatment module 20 and relies on asingle filtration and treatment unit in the water treatment module 24,the water filtration unit 40 and water filtration unit 84 are designedto be interchangeable, that is, having four chambers and a housing thatadapts to the installation requirements in module 20 and 24. In theevent that a single water filtration unit 40 only is used (nopretreatment, as in the case where the patient is traveling with themachine 22 but not the pretreatment module 20), the unit 40 is placed inthe location of the secondary filter 84. The extra carbon filtrationcapacity allows the filtration unit 40 to be used for a relatively longtime between changes. If the chloramine content of the tap water and thefiltration capacity of the carbon filtration agent are known, anestimate of the life expectancy of the filtration unit 40 can be arrivedat and the replacement of the unit 40 scheduled accordingly. Further, asample of reverse-osmosis water may be taken at a sample port in thedialysate preparation module 26 of the machine 22, e.g., at the pressurerelief and sample unit 210 (FIG.6).

II. Water Treatment Module 24

Referring now to FIG. 5, the water treatment module 24 of the dialysismachine 22 will be discussed in detail. The water treatment module 24includes a water line 70 connected to the water inlet 52 that receiveswater from the water pretreatment module 20. The flow of water into thewater treatment module 24 is controlled by a valve 72 (such as Siraipart no. D111 V14 Z723A) and check valve CV6. A thermistor 74 (10 Kohmfrom Thermometrics) and pressure transducer 76 (Microswitch part no.26PC X-98752-PC) monitor the temperature and pressure of the incomingwater in the line 72. A check valve CV1 is placed on return line 73.

A three-way valve 80 (such as Sirai part no. 311 V14 Z723A) is providedconnecting drain line 71 and inlet line 70 via return line 73. With port81 in its normally closed (NC) condition as shown in FIG. 5, water isshunted into line 82 where it is passed to a pressure transducer 76,though a bypass valve 83, to the secondary water filtration andtreatment unit 84. In the preferred embodiment, the water filtration andtreatment unit 84 is of the same basic construction and design as thewater filtration and treatment unit 40 of the pretreatment module 20. Inparticular, the housing for the secondary water filtration and treatmentunit 84 is given dimensions such that it can be interchangeablyinstalled in either the water pretreatment module 20 or the watertreatment module 24. A suitable unit 84 is the ROPAK from Millipore,part no. CPR0P0402. Referring to FIG. 3B and FIG. 5, the water is firstpassed through a first chamber 86 (86A m FIG. 3B) containing a particlefilter agent 42 and then a second chamber 88 (88A in FIG. 3B) containinga carbon filter agent 44 that removes organic matter and dissolvedgasses and any residual chlorine or chloramines in the water. The waterthen flows through a screen in the chamber 88 and through apolyphosphate water sequestering agent 43.

In the embodiment of FIG. 3B, the chambers 86B and 88B of waterfiltration and treatment unit 84 are filled with the same filtrationagents as chambers 86A and 88A, respectively. In the event that any offiltration agents in chambers 86A and 88A are exhausted, the user simplyreconnects the inlet and outlet lines from 41A and 45A to the inlet 41Band outlet 45B. This arrangement makes it relatively easy for the userto remedy the situation of an exhausted filter without having to replacean entire filter assembly, and gives the user time to make arrangementsfor the delivery of a replacement water treatment unit 40.

The treated water is then fed on output line 90 past a check valve CV2to water pressure sensor 92 (same as 76) and to an invasive conductivitycell 94 (such as the Pulsa Feeder part no. E-2A). The conductivity cell94 measures the ion content of water in the line 90.

A three way bypass valve 83 is provided on line 82 such that, during thedisinfection cycle of the machine, hot water bypasses the waterfiltration and treatment unit 84 to prevent hot water from adverselyimpacting the integrity of the polyphosphate water softening agent inthe treatment unit 84. Polyphosphate water sequestering agents are knownto degrade when subjected to water at high temperatures for an extendedperiod of time. The normally closed port NC and normally open port NO ofvalve 83 allows incoming water from the water pretreatment module 20 topass through the water filtration and treatment unit 84, but when thecondition of these ports is reversed, water is shunted through bypassline 85 to output line 90.

Still referring to FIG. 5, a pump 96 (such as Procon part no. CO16505AFVand Leeson motor no. 101389-1) is located in the line 90 to pump thewater past a pressure sensor 98 to a reverse osmosis filter 100 (such asMillipore housing part no. SLIP106M4 and Dow FilmTek XUS 50454.00filter). A flow restrictor 95 is placed across the pump 96 to avoiddeadhead failure conditions. A valve 112, flow constrictor FC2 and checkvalve CV4 are place in return line 110. An adjustable pressure regulator114 is placed in parallel with the high pressure valve 112 (Honeywellpart no. 71215 SN2 KVOONO D5D1C2). The pressure regulator 114 providesback pressure for the reverse osmosis filter 100 to force water to crossthe membrane. High pressure valve 112 bypasses flow to regulator 114minimizing back pressure in certain operating modes and failureconditions. Flow constrictor FC2 provides about 10psi back pressure toRO filter 100 during the hot water disinfection, described in detailbelow. Lines 110 and 116 are drain lines which drain water rejected bythe reverse osmosis filter 100 through valve 80 to drain line 71.

Water that passes through the reverse osmosis RO filter 100 is passedthrough a line 102, past a thermistor 104, past a conductivity cell 106(same as 94), to a three way valve 108 having a normally open port NOconnected via check valve CV14 to drain lines 109 and 116. When thenormally closed port NC of valve 108 is open, reverse osmosis water isfed via line 111 to the dialysate preparation module 26 (FIG. 1, 6).This occurs when a comparison of conductivity cells 94 and 106 verifiesproper function of reverse osmosis filter 100. If the comparison yieldsimproper function of reverse osmosis filter 100, the water is divertedto drain through the normally open port of valve 108, and lines 109, 116and 71.

Line 107 and check valve CV5 provide a pathway for the flow of drainfluids and heated water from the dialysate preparation module 26 to thewater treatment module 24. Depending on the condition of three-way valve80, fluids from line 107 are directed through line 71, or line 73. Itwill be further appreciated that the valve network in water treatmentmodule 24 permits the selective flow of water through every fluidpathway in the module 24, including a bypass of the water filtration andtreatment unit 84. Check valve CV5 further prevents water from beingpassing through the line 107 when rejected water from reverse osmosisfilter 110 is returned to drain line 71.

III. Dialysate Preparation (or Hydraulic) Module 26

Referring now to FIG. 6, the dialysate preparation module 26 will bediscussed in detail. An overall function of the dialysate preparationmodule 26 is to automatically mix and prepare the dialysate solutionsand deliver the solutions to the dialyzer 404. The dialysate preparationmodule 26 has an inlet line 200 connected to line 111 (FIG. 5) receivingfiltered water from the water treatment module 24 via valve 108 (FIG.5). The line 200 carries the water past check valve CV10 to a chemicalmixing unit 202, preferably constructed from polypropylene. A chemicaladdition and dispersion subsystem 204 is attached to the side of thetank 202 in fluid communication therewith. The loading platform 250 ofchemical addition subsystem 204 is illustrated in FIGS. 7A-7F. Thechemical applicator 260 of the chemical addition subsystem 204 isillustrated in FIGS. 8A-8C and 9A-9C. The chemical vessels (ideallybottles) 270 are illustrated in FIGS. 10A-10F.

The addition and dispersion subsystem 204 preferably includes twochemical applicators 260, each for opening a vessel 270 containing anindividual batch quantity of dialysis chemicals placed directly aboveit. One vessel 270 typically contains chemicals in liquid form and theother in powdered form. The batch of chemicals are provided inindividual batch vessels, preferably polyethylene and/or polypropylenebottles 270. When the tank 202 is filled with purified water to theproper level, the chemical applicators 260 pierce the bottles 270 frombelow with a spike, and the chemicals in the bottles fall out of thebottle by gravity into the interior of the loading platform 250. Asexplained in detail below, a sprayer 285 rinses the chemicals from theloading platform 250 into the tank 202 where the chemicals are dissolvedand mixed with water to form the dialysate solution. Additionally,bottle rinsing nozzles are preferably provided within the chemicalapplicators 260. The nozzles that are disposed below bottles containingdry dialysate chemicals eject water into the bottles in a series ofshort bursts to gradually flush the chemical out of the bottles. Afterthe chemicals are dispensed on the loading platform 250, the nozzlesflush any remaining chemicals in the bottles 270 from the bottles ontothe loading platform 250.

A third chemical applicator 260 and third vessel 270 are also preferablyprovided above the platform 250. The chemicals in the third vessel willtypically either be a salt which can be added to the dialysate solutionon demand to adjust the chemistry of the dialysate solution, or else achemical cleaning or disinfecting agent that is added to the tank duringthe disinfection cycle. Other possible chemicals for the third bottle270 are medications, and vitamins and other nutrition supplements. Asdescribed below, we prefer to use a hot pure water disinfection process,without chemicals, to clean the fluid circuits of the machine 22.However, if for some reason the hot water disinfection is notsufficient, an alternative mode may be entered whereby the disinfectingchemicals in the third vessel are added to the tank and throughout themachine to achieve cleaning and/or disinfection. Of course, additionalchemical applicators and vessels could be added to the top of theloading platform 250, if desired.

The tank inlet tube 203 is placed at the bottom of the tank 202 andoriented tangentially to the walls of the tank 202 in a horizontal planesuch that the incoming water is swirled about the side of the tank inthe direction of the orientation of the inlet 203 to create a vortex,thereby stirring the water in the tank 202. A spray washer 205 similarto a dishwasher sprayer is provided in the upper region of the tank 202,and is operative during cleaning of the tank 202 and mixing of thedialysate chemicals the tank 202. The force of the water through spraywasher 205 causes the spray washer 205 to rotate and spray water intothe tank 202 in the same direction as the flow of water in the vortexcreated by water inlet 203. The cooperation of the spray washer 205 andwater inlet 203 create good mixing action in the tank 202, promotingeffective dispersion and dissolution of the chemicals that have beenintroduced into the tank 202 from the loading platform 250, andpreventing the settlement of chemicals on the bottom of the tank.

The tank 202 itself is preferably made from a lightweight,biocompatible, chemically compatible, and sterilizeable andsubstantially non-compliant (i.e., rigid and not susceptible toexpansion or contraction due to pressure, temperature or othercondition) material, that is given the shape shown in FIG. 6. Othershapes are of course possible. We have determined that a tank made frompolypropylene with the shell reinforced with fiberglass windings on theoutside of the shell meets these requirements for the present dialysisapplication. The polypropylene is chosen because of its chemicalinertness, light weight and ability to be exposed to hot water for longperiods without any effect. An alternative material for the shell ispolyvinylidene fluoride (PVDF). The reinforcing fiberglass threadssignificantly improve the non-compliance (or stiffness) of the tank 202.As discussed in detail below, non-compliance of the tank is importantfor improving the accuracy of the ultrafiltration of the patient (i.e.,the real-time measurement of fluid removed from the patient duringdialysis). The fiberglass threads are wound around the exterior of thewalls of the tank 202 in overlapping diagonal layers, with an additionallayer wrapping about the mid-section of the tank 202 in a horizontalmanner. A suitable tank can be obtained from Structural North America inOhio. Other possible reinforcing fibers may be suitable, such ascomposite fibers, carbon fibers and kevlar, which may be integrated intothe shell body itself or wound on the outside of the shell.

A pressure transducer LT (Microswitch part no. 26PC X-98493-PC) isprovided at the bottom of the tank 202 in line 206 for the purpose ofdetermining the level of water in the tank 202. Line 206 is isolated(static, with no fluid flowing through the line) when the NO port ofvalve V17 for line 206 is closed and the NC port in line 209 is open,permitting the level transducer to read the level in the tank 202. Thiswould be the case when the tank 202 is being filled. During the fillingand mixing of the tank, water is circulated from the line 209 to V17 toV9 through pump 212, valves 220 and 232, line 231 to valve V15, andsprayer 205 in the tank 202, which assists in the mixing of the tank202.

The tank 202 has a polypropylene mesh filter FTB (130 micron) moldedinto a flat plate with a polypropylene frame at the bottom of the tank202. A pump filter FP2 (preferably 50 to 200 microns) is placed on thedegassing line 209. Any air or gas which may have been introduced intothe dialysate is removed by pumping the dialysate through the filterFP2. The filter FF2 creates a negative pressure which causes entrappedair to come out of the water.

The tank outlet line 206 carries dialysate solution past a pressurerelief/sample port 210 to a pump 212. The pressure relief/sample port210 is a combination pressure relieve valve and integral sample removalport of the same design as pressure relief/sample port 78 (see FIG. 4),and is used to prevent over pressure of the tank 202 and to take fluidsample from the system. When the chemicals are released from thechemical addition subsystem 204 to the tank and are being mixed in thetank 202, the circulation of fluid is though line 206 (with degassingline 209 static).

A three-way valve V17 is placed at the intersection of lines 206 and 209and determines which line 206, 209 is static. The pump 212 (such asMicropump EG series, 0-3 L/min.) pumps the solution past a pressuretransducer 214 (Microswitch PN 26PC X-99752-PC), an integral pressurerelief valve with sample removal port 615, and a thermistor 216 to anoninvasive conductivity cell 218 which detects the concentration ofions in the line 206.

The noninvasive conductivity cell 218 is illustrated in detail in FIG.11A. The inlet line 206 is divided into first and second fluid channels221 and 222 integral with the inlet line 206. The channels 221 and 222branch in directions 90 degrees from each other. The channels are eachoriented at an angle of approximately 135 degrees relative to the inletline 206. The channels 221, 222 form s rectangular loop with the inletline 206 and the outlet line 223 at opposite corners. A conductivitymeasurement sensor (e.g., Great Lakes no. 697 E sensor) 224 with leads225 is circumferentially disposed about one of the fluid channels 222;The leads 225 from the sensor 224 are fed to the central processing unit610 or 616 of the user interface and control module 25 (FIG. 16). Analternative construction is shown in FIG. 11B, where channels 221A and222A are shorter than channels 221 and 222. With either construction,the conductivity cell 218 is preferrably installed in a vertical orvertically inclined orientation such that fluid flows upwards throughthe channels 221 and 222 which prevents the entrapment of air bubbles inthe fluid line 222.

The construction of FIG. 11B provides a minimum path-length tocross-sectional area ratio for the fluid channels 221 and 222. Thisconstruction generally maximizes the sensitivity of the sensor 218 andreduces response time.

Referring again to FIG. 6, a three-way valve 220 controls the flow offluid through output line 226 and return line 236. Water or solution inline 226 is fed to a heater assembly 228. Heater assembly 228 is atemperature controlled, 1300 watt, flow-through heater, such as theHeatron no. 23925 heater. The heater assembly 228 is used for heatingdialysate up to body temperature as it is passed to the extracorporealcircuit module 28 (FIG. 1). The heater is also used for heating water upto a disinfection temperature of at least 80 degrees C., and preferablyat least 85 degrees C., and maintaining the water at that temperaturefor more than an hour during the water disinfection of the fluid pathsof the machine 22, as discussed in detail below. A thermistor 230monitors the temperature of the fluids in the line 226. A three-wayvalve 232 controls the flow of fluid through the tank return line 231and the output line 233. A dialysate filter such as ultrafilter/pyrogenremoval filter 234 is provided for removal of any pyrogenic materialsand particulate matter from the dialysate. Suitable filters 234 are theMinntech pyrogen filter and the Fresenius F-80 filter. No dialysatesolution goes to the dialysate circuit 402 during dialysis treatmentwithout first passing through the filter 234. The condition of three-wayvalve 236 controls whether fluid exits from the ultrafilter/pyrogenfilter through line 238 or out dialysate circuit input line 406. A flowmeter 241 (Xolox part no. 2831F6FF) measures the flow rate of thesolutions in line 406.

A check valve CV12 is placed between line 238 and 206. Line 238 andcheck valve CV 13 allow air to come out of the dialysate side of theultrafilter 234 (i.e., the outside of the fibers in the filter 234)during the priming of the ultrafilter 234 and pumping of dialysatethrough the ultrafilter 234 to the dialysate circuit 402.

We have devised a pre-treatment fiber bundle integrity test for thepyrogen/ultrafilter 234. The integrity of the ultrafilter 234 isimportant to insure that there are no leaks. The pyrogen/ultrafilter ispressurized on the "blood" or dialyzer side (that is, the interior ofthe fiber bundles in direct fluid communication with the dialyzer 404)of the ultrafilter 234 prior to dialysis, and the rate of pressure decayis measured. A rapid pressure decay, or inability to pressurize thepyrogen/ultrafilter, will cause an alarm to sound, warning the patientof the need to replace the pyrogen/ultrafilter 234. To accomplish this,we first evacuate fluids from the blood side of the pyrogen/ultrafilter234 by operating the UF pump 242 in the reverse direction to pump airback through the valve 236, through bypass valve 412 in the dialysatecircuit 402, through line 406 into the lumen or blood side of thepyrogen/ultrafilter 234. Once water has been evacuated from the bloodside of the pyrogen/ultrafilter 234, the blood side starts to pressurize(assuming there are no leaks in the pyrogen/ultrafilter 234). The UFpump 242 pumps until the pyrogen/ultrafilter 234 is pressurized to 500mm Hg. If there are any leaks, air will leak into the dialysate side ofthe filter 234. The air pressure is measured with the pressure sensor410 in the dialysate circuit 402. If pressure sensor 410 neverpressurizes, then a severe leak is present. A slow decay in pressureindicates there is no leak. The rate of decay indicative of a leakrequiring replacement of the pyrogen/ultrafilter is a function of thephysical properties of the filter's membrane, and will accordingly varydepending upon which filter is used. For most filters 234, we expect thethreshold decay rate indicative of a failure to be greater than 10-25 mmHg/30 seconds, depending on the type of filter.

The pressurization of the pyrogen/ultrafilter 234 can also be correlatedto the maximum pore size of the filter. As the pyrogen/ultrafilter 234is pressurized to higher and higher pressures, a maximum pressure willbe reached above which the pressure drops suddenly indicating that thesurface energy of water in the pores of the filter is less than theforce due to the pressure. By knowing the pore size from the maximumpressure, the filtration capacity for certain pyrogens and othermaterials may be determined.

Referring to FIG. 16. it will be appreciated that the analog board 614and central processing unit 610 of the central control module receivethe pressure data from the pressure sensor 410. Pressure readingsindicative of a leak, such as where the rule of decay is greater than apredetermined threshold limit, will cause the CPU 610 (or safely CPU616) to issue an alarm, such as by issuing a message on the patientinterface, or activating the audio or visual indicators 604 or a buzzer.

During the filling of the tank 202, after the chemicals are added, themachine 22 determines when to stop adding water to the tank bymonitoring the fluid sensor 288 in the line coming out of the top of thetank 202. When fluid sensor 288 sees fluid, the flow of water is stoppedby closing off valve 108 (FIG. 5).

The return flow of old solution (i.e.; solution that has passed throughthe dialyzer) from the dialyzer 404 is through return line 240, valveV18 and dialysate inlet 243. Valves V19, V15 and V6 are closed,directing dialysate through to the dialysate inlet 243.

We have invented a technique of maintaining the separation of new andold dialysate in the tank 202 by taking advantage of the differences indensity in dialysate when the dialysate is at different temperatures.Our technique is an improvement over the technique described in theTerstegen Patent, U.S. Pat. No. 4,610,782. The preparation and mixing ofdialysate in the tank 202 takes place with the dialysate at atemperature of 28 to 30 degrees C. controlled, in the preferredembodiment, by the temperature-controlled mixing valve 38 in the waterpretreatment module 20. During dialysis, dialysate is heated in theheater 228 to body temperature, generally 37 degrees C., and sent to thedialyzer 404 in the extracorporeal circuit module 28 (FIG. 13). New(i.e., fresh) dialysate is withdrawn from the bottom of the tank 202 andold dialysate is returned at the top of the tank 202 in inlet 243 at atemperature of about 37 degrees C., or perhaps a degree or two coolerdue to radiative and conductive heat loss in the tubing and hardware inthe dialysate circuit 402. The old dialysate is returned to the top ofthe tank 202 in a manner so as to substantially prevent turbulence ofthe old dialysate, that is, in a manner to gently introduce the olddialysate into the top of the tank to prevent mixing of the old and newdialysate. We accomplish this by orienting the inlet 243 slightly upwardand towards the aide walls of the tank 202. The old dialysate forms azone above the new dialysate with a thermocline boundary layerseparating the old and new dialysate due to the temperature differential(and resulting density differential) between the dialysate in the twozones. As the dialysis process continues, the boundary zone migratesdown the tank 202 as the volume of fluid in the upper zone of olddialysate increases and the volume of fresh or new dialysate diminishes.

This method works best when the temperature differential between theupper zone and lower zone is at least 5-7 degrees C., or great, but willwork acceptably down to 3 degrees C. Ordinarily, this differential willbe present when the dialysate is heated as described.

An improvement to this technique is to heat one to two liters of newdialysate above the temperature of the dialysate in the tank 202 (bypreferably at least 5 degrees C.) prior to the initiation of dialysis,and introducing the heated dialysate into the top of the tank in asubstantially non-turbulent manner. This sets up the temperaturedifferential zones such that when the old (used) dialysate in introducedinto the tank, it enters the upper zone, further minimizing thelikelihood of substantial mixing of the old and new dialysate. Theheating can be performed by heater 228, and the return of the heateddialysate is through valve 232, return line 231 and valve V18. ValvesV6. V15 and the NO ports of vanes 236 and 232 should be closed to directthe heated dialysate into the tank 202.

The separation of old and new dialysate in the tank 202 offers a numberof advantages. First, it allows a closed loop ultrafiltration controlmethodology to be used. Second, the fluids being dialyzed from thepatients are collected in the tank 202 separate from other solutions,permitting the old dialysate to be sampled measured, and visuallyobserved in a tank with a window or a sample-removal port. Thirdly, theclosed loop ultrafiltration permits the machine to operate, duringdialysis, without the machine being connected to a water source and adrain. This gives more mobility to both the machine 22 and the patient,a future particularly advantageous in the hospital, home and nursinghome environments. Fourthly, separation of old and new dialysateimproves the efficiency of clearance of uremic toxins for a batchsystem.

A UF (ultrafiltration) pump 242, connected to the return fine 240through valve 236, pumps dialysate solution to and from the UF tank 244,the direction of flow being a function of whether the UF pump 242 isoperated in a forward or reverse direction. NC port of valve V9 isclosed and NO port of valve V13 is open providing the pathway for thesolution to enter the bottom of the tank 244. The UF pump 242 is alsoused to pump prime solution from the extracorporeal circuit 400 back tothe UF tank 244.

The UF tank level sensor LUF precisely measures the fluid volume in theUF tank 244. The UF tank 244 is used to store fluid removed from thedialysate circuit commensurate with the fluid removed from the patient.The fluid removed from the patient is the difference in the volume offluid in the UF tank before and after the dialysis of the patient'sblood in the dialyzer. The rate of fluid removal into the UF tank 244(and hence water volume when multiplied by time) is controlled by thepump rate of UF pump 242. A sterile barrier air filter AF (such as PallEMFLON II) open to the atmosphere is installed at the top of the tank244. Background information on ultrafiltration control in hemodialysisis described in U.S. Pat. Nos. 3,974,284 and 3,939,069 assigned toRhone-Poulene (both now expired), which are incorporated by referenceherein.

A pressure transducer LUF is mounted at the bottom of the UF tank 244.The transducer LUF measures the pressure and hence level of fluid in thetank 244. The level sensor LUF acts as a safety backup and watchdog forthe UF pump 242 to verify the amount of ultrafiltration during dialysis.Specifically, the sensor LUF measures the hydrodynamic pressure ofdialysate in the ultrafiltration tank 244 and responsively generates ameasurement signal (sent to the control module 25) indicative of thevolume of fluid within the UF tank 244. The rate of transport of fluidby UF pump into the UF tank 244 is continuously monitored, such as byknowing the output volume per revolution of the UF pump, and the timeelapsed during dialysis. This information allows the central controlmodule 25 (FIG. 16) to determine the expected volume of dialysate in theUP tank 244. By comparing the measurement signal from the sensor LUFwith the expected volume of dialysate in the UP tank, the pump rate ofpump 242 is verified.

In one possible implementation of this technique, a decision as to theadjustment of the dialysate transport rate into the UP tank (i.e., thepump 242's pump rate) can be made. For example, if sensor LUF indicatesthat there is 350 ml of fluid in the tang 244 but a calculation of theexpected volume of fluid in the UF tank based on pump rate and elapsedtime is 385 ml, the pump 242 is pumping about 10% to slow and the pumpspeed should be increased to meet the ultrafiltration target in theexpected dialysis time.

We calibrate the UF pump 242 each time before dialysis commences usingthe flow meet 241 to insure ultrafiltration control. After the tank 202and fluid circuits of the dialysate preparation module 26 have beenfilled with dialysate, positive pressure is created with pump 212 inline 209. Dialysate is conducted from tank 202 through valve V9, throughUF pump 242, to valve 236, down through CV12, line 206, valve 220, valveV8 and into pyrogen/ultrafilter 234. The dialysate is sent up throughflow meter 241 to the dialysate circuit 402, where the solution goesthrough bypass valve 412, through return line 422, line 240, valve V18and back to the tank 202. The pump rate of UF pump 242 can now becalibrated by the control module 25 against the reading of the flowmeter241. During dialysis, dialysate is pumped from the dialysate circuitinto the ultrafiltration tank 244 via line 240, valve 236 and valve V13in accordance with the target ultrafiltration volume for the patient.

Air and drain paths 282 and 280 are provided in the module 26 forcollecting any fluid or overflow from the tank 202. An optical fluidsensor 288 is used to detect when the tank 202 is full during the tankfill mode, to detect failure of valve V6 during dialysis, and to detecta full tank during the disinfection cycle, by detecting water ordialysate in the hose portion (solid line) from valve V6 to air filterAF.

In our design, the housing of the dialysate preparation module 26includes a floor or base for the entire machine 22, including the othermodules 24 and 28. Any fluid such as blood, water or dialysate thatleaks from the modules 24, 26 or 28 collects in a catchment basin 284 atthe bottom of the entire machine. Leaks will drip on any arbitrary path,shown schematically as broken lines 280 and 282. The floor of thehousing for the machine 22 is horizontally non-planar to facilitate thecatchment of fluid, in a fashion similar to an oil pan for an engine.The floor of the machine may be bowl shaped or given any other suitablecontour to provide a lower catchment basin 284. A fluid sensor 286 isplaced in the vicinity of the catchment bash 284 to detect the presenceof fluid in the catchment basin 284. If fluid is detected, the user isalerted by an audio or visual indicator, and the machine is checked forleaks.

Referring now to the left-hand side of FIG. 6, a line 283 is providedfor conducting water to the chemical application system 260 for rinsingthe dialysate chemical bottles 270 after they have been opened, and fordisinfection of the bottle's seal. Line 281 is a return line from thechemical application system 260 to valve V13. Line 291 also provideswater from three-way valve 287 to a fountain or sprayer 285 in thechemical loading platform 250. Drain lines 236 and 236A provide apathway for dialysate or disinfection water to exit from theextracorporeal circuit module 28 via the disinfection manifold 494 (seeFIG. 36 also) through valve V14, and thermistor 293. Lines 289 and 289Aprovide a fluid pathway into the extracorporeal circuit module 28 viavalve CV11. Line 295 connects the disinfection port 495 of thedisinfection manifold 494 (FIG. 36) via line 496. Thermistor 293monitors the temperature of the fluid returning from the extracorporealcircuit 400 during the hot water disinfection cycle.

A. The Chemical Loading Platform 250

The chemical loading platform 250 of FIG. 6 is illustrated in detail inFIGS. 7A-7F. FIG. 7A is a perspective view of the platform 250 shownpositioned against the side of the tank 202. FIG. 7B is a top plan viewof the platform 250. FIG. 7C is a sectional view of the platform 250along the lines 7C of FIG. 7B. FIG. 7D is a sectional view of theplatform 250 along lines 7D of FIG. 7B. FIG. 7E is an elevational viewof the platform 250. FIG. 7F is a sectional view of the platform 250along the line 7F of FIG. 7E. In the figures, the platform 250 is anintegrally molded housing mounted to the side of the tank 202 and havinga top 304 with four apertures. Apertures 306, 308 and 310 providepassageways for chemicals from the chemical application assemblies 260which are installed above the top 304 of the platform 350. Aperture 312is for a line 291 (FIG. 6) to provide water to a sprayer 285 suspendedwithin the platform 250 for rinsing chemicals from the shelf 320 intothe tank 202. (See FIG. 6). Shelf 320 is inclined at an angle of between10 and 30 degrees (preferably 17 degrees) relative to the horizontal topromote dispersion of chemicals delivered onto shelf 320 into the tank202. Note that the tank 202 has fiberglass windings 314 wrapped around apolypropylene shell 316.

The platform further has a rim 302, 326 and sidewalls 318 and 319. Thechemicals are placed in fluid communication with the interior of thetank by virtue of the open side 324 of the platform 250, which isaligned with an opening (not shown) in the tank 202.

Referring to FIG. 6. and 7D, the sprayer 285 sprays fluid (e.g.dialysate or purified water) in the direction of the lower shelf 320 toassist in washing dialysate chemicals off the shelf 320 and into thetank 202, thereby promoting effective dissolution of the chemicalswithin the tank 202 and the avoidance of buildup of chemicals on theshelf 320.

Referring in particular to FIGS. 7C and 7D, an aluminum plate 322 ismounted to the top of the platform 250 to provide a mounting base forthe chemical application assemblies 260 (FIGS. 6, 8A-8C).

B. The Chemical Applicator 260

Referring now to FIGS. 8A-8C, the chemical applicator 260 will beexplained in detail. The chemical applicators 260 (three in all in thepreferred embodiment) are installed on the aluminum plate 322 directlyabove the apertures 306, 308, 310 (FIG. 7A). FIG. 8A is an elevationalview of the applicator 260, and FIGS. 8B and 8C are sectional views ofthe applicator 260 with the spike 330 in upper and lower positions,respectively. When the spike 330 is in the upper position (FIGS. 8A and8B), the tip 331 of the spike pierces the bottle 270 which is installedin an upside-down orientation in the upper region 332 of the applicator260, causing the chemicals in the bottle 270 to pour out through theapplicator 260 and apertures 306 (or 308 or 310) and onto the shelf 320of the loading platform 250 (FIG. 7).

The applicator 260 has a cylindrical housing 334 mounted to a basemember 336 affixed to the aluminum plate 322. The housing 334 has anopen interior region 338. A threaded drive region 338 between upper andlower positions. The spike 330 pierces the seal on the bottle 270 orother vessel containing the dialysate chemicals (of other contents ofthe bottle 260) when the spike 330 is moved to the upper position (FIG.8B). The spike 330 has an integral cylindrical body 342 concentric withthe housing 334 with an open interior for permitting passage ofdialysate chemicals therethrough after the spike 330 has pierced theseal of the bottle 270. A pair of thread blocks 344 are mounted to theside walls of the spike 330 which engage the threads 346 on the drive340. A drive belt 340 (one or two) or other suitable means (such as acog) engages the threaded drive collar 340 (FIG. 8A). As the belt 348rotates the collar 340, the thread blocks 344 are rotated, causing thespike 330 to move between the upper and lower positions depending on thedirection of movement of the drive belt 348.

Referring in particular to FIGS. 8B and 8C and FIG. 12, a nozzle 350 isdisposed within the cylindrical housing 334 in communication via line281 with the water inlet line 200. The cylindrical body 342 of the spikehas a vertical slit to accommodate the nozzle 350. The tip 352 of thenozzle 350 is oriented upward in the direction of the bottle 270 whenthe bottle 270 is mounted to the housing 332. The flow of water throughthe nozzle 250 on demand ejects water towards the interior of the bottle270 after the bottle has been opened by the spike 330, thereby rinsingthe interior of the bottle 270 and promoting the release by gravity ofthe entire contents of bottle 270 through the aperture 306 (or 308, 310)and into the tank 202. To control the dispensing of dry dialysatechemicals from the bottle, and prevent clogging of chemicals at the baseof the bottle, we prefer to pulse water through the nozzle 350 over aperiod of time. For example, we pulse water through the nozzle for onesecond (with a pressure greater than 10 psi), then pause briefly whilesome of the chemicals fall through the interior of the spike 330, thenpulse again, pause, and then continue the process until all thechemicals have fallen out of the bottle. This pulsing may occur forperhaps 50 times over a ten minute period. This pulsing action preventsall of the chemicals from being dumped at once onto the shelf of theloading platform. When the bottle is substantially empty, the nozzlerinses out the bottle with a continuous stream of water of 5 to 10seconds duration.

The nozzle 350 also ejects heated water (or water treated withdisinfecting chemicals) onto the outside surface of the seal 372 of thebottle 270 during the disinfection cycle of the machine, therebydisinfecting the interface between the chemicals in the bottle 270 withthe dialysate preparation tank 202.

An O-ring 329 is provided around the base 335 of the spike 330. When thespike is in the lower position, outlet tube 337 leading to line 281(FIG. 6) is open and the tank 202 is closed off through ports 306, 308and 310.

C. The Chemical Vessel (Bottle) 270 and Automatic Identification System

Referring now in particular to FIGS. 8C and 9A-9C. together with FIG.10A, a bottle mounting member 354 is place above the housing 334 of theapplicator 260 to insure that the bottle 270 is mounted in alignmentwith the spike 330 to the applicator 260. The mounting member 354 isshown in a top plan view in FIG. 9A (i.e., as it would be seen whenlooking down from above in the direction of the top of the spike), in abottom plan view in FIG. 9B, and in side elevational view in FIG. 9C.The mounting member 354 has a central opening 360 through which the headof the bottle 270 is inserted. A button through hole notch 356accommodates a touch button 362 (FIG. 10A) containing coded informationas to the contents of the bottle 270 that is affixed to the neck of thebottle 270. The touch button 272 is about a half inch in diameter. Themember 354 has a pawl 357 (that is retractable by operation of anelectric solenoid 358) for automatically removing the touch button 362when the bottle 270 is removed from the mounting member 354.

During installation of the bottle 270, the head of the bottle 270(turned "upside down") is placed within the opening 360 and rotated inthe direction of the arrow of FIGS. 9A and 9C. The touch button 362slides past the pawl 357 into contact with a touch button reader. Whenthe bottle 270 is removed from the applicator, the bottle must berotated in the opposite direction. Pawl 357 is activated by solenoid 358to an extended position. When the bottle is rotated such that the touchbutton is rotational pawl the pawl 357, the pawl 357 pushes the touchbutton 362 off of the bottle 270, causing the touch button to fall. Asuitable catchment structure is provided about the applicators 260 andaluminum shelf 322 (FIG. 8) to catch and collect the fallen touchbuttons. The user of the machine 22 collects the buttons and sends themback to a collection center for reprogramming and reuse. Alternatively,the buttons 362 could be collected by a service technician during aservice visit.

The structure of the bottle 270 is shown in detail in FIGS. 10A-10F.FIG. 10A is an elevational view of the bottle 270 with the touch button362 removably affixed to the neck region 364 of the bottle 270. FIG. 10Bis a sectional view of the neck region 364 of the bottle 270 showing thepolyethylene or polypropylene shell 380 and a polypropylene cap 370snapped onto the shell 380 via circumferential complementary snapelements 382. A polypropylene seal 372 integral with the cap 370 closesoff the bottle 270. Polypropylene is chosen for the material for the cap370 since the cap 370 is subject to hot water disinfection during thedisinfection cycle of the machine 22. Specifically, when the bottle 270is installed within the mounting member 354 above the applicator 260,hot water is applied via nozzle 350 (FIG. 8C) to the exterior surface ofthe polypropylene seal 372. While polyethylene is a preferred materialfor the bottle shell 380, it tends to soften when subjected to hot waterfor an extended period of time.

FIG. 10C is a detailed elevational view of the upper portion of thebottle showing the pinch semicircular rim 366 that retains the touchbutton 362. FIG. 10D is similar to FIG. 10C with the cap 370 rotated 90degrees. A retaining bead 368 helps keep the touch button 362 in place.FIG. 10E shows the opposite side of the cap 370 from FIG. 10C. Thethreads 367 engage the upper portion of the housing 334 of theapplicator 260 (FIG. 8).

FIG. 10F is a plan view of the seal area 372 of the bottle 270. The seal372 comprises a frangible section 374 and a hinge section 376. Themounting member 354 (FIG. 9), and in particular the notch 356, acts as ameans for insuring that the bottle 270 can be inserted only one way ontothe applicator 260 and aligning the upper tip of the spike with thefrangible section 374 of the seal opposite the hinge section 376, sothat the tip 331 of the spike 330 (FIG. 8B) contacts the region 384 ofthe seal 372. The uppermost rim of the spike 330 tears through thefrangible section 374, with only the hinge portion 376 uncut, when thespike 330 is moved to its upper position (FIG. 8B). By virtue of thestiff properties of the polypropylene material, and by virtue of thesupport from the spike 330 from below when the spike 330 is in theupward position, the broken seal 372 maintains an generally upwardorientation, allowing the chemicals in the bottle 270 to exit from thebottle 270 and permitting the nozzle 350 to spray into the interior ofthe bottle 270 to rinse out any remaining chemicals in the bottle 270.The rinsing action of a bottle 270 containing dry dialysate chemicals isshown in FIG. 12.

When the bottle 270 is mounted to the applicator 260, the touch button362 is placed in touching contact the a touch button reader mounted inany suitable fashion above the applicator 260. The ruder retrievesinformation coded in the button 362 (such as the contents of the bottle,a date code, a lot code, and other information) and passes theinformation to the central processing unit of the control module 25(FIG. 1). The control module 25 has a memory storing information such asthe correct dialysate chemicals for the patient, the patient's dialysisprescription, and software for processing the information from the touchbutton. If the bottle is not the proper chemical for the patient, thecontrol module 25 alerts the user, such as by activating a suitablealarm. The user, thus alerted, removes the incorrect bottle 270 prior tocommencement of the next dialysis procedure and replaces the bottle 270with the proper bottle, and the process goes forward. Touch buttons,readers and supporting materials suitable for use with the presentinvention can be obtained from the Dallas Semiconductor Corp., 4401 S.Beltwood Parkway, Dallas Tex. The above-described identificationtechnique promotes safety and the prevention of unintentionalintroduction of the wrong dialysate chemicals into the tank.

It will be appreciated that other types of indicators besides touchbuttons may be applied to the bottles such that the indicator is read bya machine when the bottle is about to be used. For example, bar codes,two and three dimensional bar or dot matrices, radio frequency transmitsor magnetic strips may be affixed in any suitable fashion to the sidesof the bottles and read by the appropriate machine in a well knownmanner. Ideally, the reading occurs during or immediately afterinstallation of the bottle and prior to the opening of the bottles andintroduction of the chemicals to the tank 202, so that in the case thatthe wrong bottle was installed, the patient is alerted and correctiveaction can be taken.

D. The Dialysate Circuit 402

The dialysate preparation module 26 further includes a dialysate circuit402 that circulates dialysate from the tank 202 to the dialyzer 404 andback. The dialyzer 404 (such as the Fresenius F-80 filter) filters bloodto remove toxins and excessive water buildup in the patient's blood. Thepatient's blood is introduced into the machine via the extracorporealcircuit 400 (FIG. 13).

The inlet line 406 carries dialysate solution to a thermistor 408, whichmonitors the temperature of the fluids in the line 406. A pressuretransducer 410 (Microswitch 26PC X-98752PC) monitors the pressure in theline 406. Bypass valve 412, and input and output valves 414 and 416control the flow of dialysate unto and out of the dialyzer 404 via inputline 418 and output line 420.

During dialysis, the thermistor 408 data is fed to the safety CPU 616(FIG. 16) to insure that the temperature of the dialysate is less than amaximum critical temperature, in the present example 39 degrees C. Ifthe temperature is greater than the critical temperature, the safety CPU616 closes off valves 414 and 416 and opens up bypass valve 412.Conductivity sensor 218 data (FIG. 6) is also fed the safety CPU 616 andif abnormal conductivity readings are sensed, the valves 414 and 416 areclosed and bypass valve 412 is opened.

The return flow of old dialysate is via line 422. A noninvasiveconductivity monitor 426 (same as item 218, FIG. 11) and a blood leakdetector 428 are provided in the line 422. Blood leak detector 428detects a leakage of blood from the dialyzer 404 into the dialysate. Thepresence of blond in the line 422 also causes valves 414 and 416 to doseand valve 412 to open, to prevent any additional loss of the patient'sblood.

E. The Blood Leak Detector 428

Background information on blood leak detectors known in the prior an canbe found in U.S. Pat. Nos. 4,925,299; 4,166,961; 4,087,185 and4,017,190, the contents of which are incorporated by reference herein.Our presently preferred design, based on absorbency of light by theblood, is shown in schematic form in FIG. 25A. A light emitting diode(LED) 530 is pulsed between an OFF condition and an ON condition, duringwhich it emits light at which the absorbency of the light by blood is ata maximum, such as 880 nm. The light from the diode 530 passes through amirror-coated beam splitter 532. The resulting light of intensity P issplit into two portions. One portion is directed toward a referencephotodiode 534, and the other portion is directed through a chamber orcuvette 536 containing dialysate solution and onto a second blooddetector photodiode 538 identical to the reference photodiode detector534. The reference photodiode 534 also receives light from externalinterfering light sources P_(EXT2) directed onto the diode 534. Thereference diode 534 is used for generating a light intensity correctionfactor, as discussed below. Photodiode 534 is connected to anoperational amplifier 540 having a resistor 542. The output voltage ofthe op. amp. 540 is represented by V_(PD2).

External interfering light sources P_(EXT1) also impinge on thephotodiode detector 538. The photodiode detector 538 is connected tooperational amplifier 546 having resistor 533 connected across theoutput and negative terminals as shown. The resulting output voltagesignal is represented by V_(PD1). Suitable beam splitter and opticaldiffusing glass components for the detector of FIG. 25A can be obtainedfrom Edmund Scientific Co., of Barrington, N.J.

The housing for the blood leak detector (not shown) is constructed so asto deflect any air within the cuvette 536 away from the light path 535.Curved retry paths or baffle plates may be used for this purpose. Thegoal is to prevent air bubbles for adhering to the transmitting andreceiving windows 537 and 529, respectively on the sides of the cuvette536. Maintenance of turbulence of the fluid within the cuvette 536should accomplish this, but the above-cited blood leak detector patentsdisclose additional techniques for the avoidance of air-bubbles alongthe light path of a sensor.

The signal flow of the blood leak detector 428 of FIG. 25A is shown inFIG. 25B. The following is a table of the legends used an FIG. 25B.

P=LED 530 Light Intensity

K_(C) =Light Attenuation of Cuvette 536 and Dialysate

K₃ =Attenuation Coefficient Due to Blood in Dialysate

P_(EXT1), P_(EXT2) =External Internal Light Sources

K_(PD1), K_(PD2) =Photodiode 538, 534 Sensitivity Coefficients,respectively

V_(OFF1), V_(OFF2) =Electronics Offset Coefficients for 546, 540,respectively

V_(PD1) =(P·K_(C) ·K_(S) +P_(EXTI)) K_(KD1) +V_(OFF1)

Prior to dialysis, a control solution consisting of dialysate solutionfree from blood is introduced into the cuvette 536, the light source 530is pulsed on and off and measurements of the light intensity in thereference and blood leakage photodetectors 534, 538 respectively aremade. The measurements during the light off condition are stored andsubtracted from the next light-on measurement. The process is repeatedduring the conduction of dialysate solution from the dialyzer 404 duringdialysis. A calculation of an attenuation coefficient indicative of thepresence of blood in the dialysate is made repeatedly during dialysis,and an alarm is sounded if blood is detected. The provision of thereference detector 534 permits the removal of any offset or driftconditions in the electronics or variation in the light intensity fromthe light source 530.

The photodiodes 534, 538 must be shielded from extraneous light sourcessuch as incandescent bulbs or fluorescent lights. Any residual lightappearing on the detectors P_(EXT1) and P_(EXT2) is low-pass filtered.The filtering passes only the DC component of the extraneous signal. TheDC component of the extraneous signal is removed in the on-off pulsingthat removes electronic offset and drift.

Any additional light paths from source to detector must also beminimized. Light paths other than that through the dialysate will causethe measurements to deviate from the expected levels for a givenconcentration. This cannot be corrected since the offset measurement istaken with the light source off. The extraneous light path can bemeasured by a given cuvette by replacing the dialysate with a fluid ofvirtually no light transmittance. Then the light source is varied from 0to maximum output and the detector output monitored.

The blood concentration measurement is as follows. Prior to treatment,the light intensity at the photodiode detectors 538 and 534 is measuredbefore the dialysis treatment. ##EQU1##

During treatment, the light intensity at the detector 538 is measured.The ratio of the intensity before treatment over the intensity duringtreatment is computed. In addition, the reference photodiode detector534 is measured to correct the intensity readings during treatment fromoffset, drift, and extraneous light sources. Measurements andcalculations are as follows: ##EQU2## The attenuation coefficient due tothe presence of blood in the dialysate, K_(S), is as follows (assumingK_(C), K_(PD1) are constant during the treatment): ##EQU3##

Suppose that the light intensity from the LED 530 increased 50% afterthe initial measurements prior to dialysis were made, for whateverreason. The attenuation coefficient K_(S) is the same. Themanufacturers' variations for light intensity P, photodiode sensitivityK_(PD1) and K_(PD2) will not effect the calculation of the attenuationcoefficient, since they cancel out. Thus: ##EQU4##

The reference detector 534 is used for correction: ##EQU5##

O Attenuation Calculation (If K_(C), K_(PD1), K_(PD2), Constant DuringTreatment) ##EQU6##

It will additionally be noted that the above calculations of K_(S)assume the beam splitter 532 is a 50% splitter directing light in twopaths of equal intensity P. A different ratio of the light intensitycould be used with a conversion factor used in the K_(S) calculation.

If the sensitivity of the diodes 534 and 538 varies differently fromeach other during the treatment, then the attenuation coefficient K_(S)will vary. This situation will be avoided by choosing the same type ofphotodiode detectors 534, 538. Additionally, the photodiode

The blood leakage detector can be tested by varying the intensity of thelight source 530 and making sure that the reference and blood sensorphotodiode detectors, 534 and 538, respectively, track within limits.The supporting electronics for the blood leakage detector 428 should below-noise with high stability. Calibration tests must be performed todetermine the expected light levels detected for various dialysate flowrate and blood concentrations. The path length of the light within thecuvette determines the sensitivity of the optical density measurements.

As an alternative approach, instead of pulsing the light from LED 530 onand off, the light intensity can be sequenced OFF, LOW and HIGH. If ablood concentration in the cuvette 536 causes a low reading near thenoise floor of the electronics, the next higher detector readingcorresponding to the high light source intensity can be used.

IV. The Extracorporeal Circuit Module 28

Referring now to FIGS. 13 and 27, the extracorporeal circuit module 28will be described in detail. The patient's blood is introduced into theextracorporeal blood circuit 400 in arterial line 432. If a saline bag448 is used as discussed below, the saline is introduced into thearterial line 432 at three-way connector TC with rotating male luer lockand two female luer lock such as Haemotronics Part No. B-82 or,alternatively, a four-way injection site with rotating male luerlock/double female luer lock, such as Haemotronics Part No. CR-47. Thesaline bag 448 is optionally provided, and is connected to the arterialline 432 by a saline infusion line S having an optical fluid sensor 781and a clamp 779. The saline bag 448 has several potential uses: forpriming air out of the extracorporeal circuit 400, for replacing lostfluid during therapy and rehydrating the patient, and for rinsing backblood to the patient. Our reverse osmosis water and ultrapure dialysate,introduced to the extracorporeal circuit 400 by causing a pressuredifferential to exist at the membrane of the dialyzer, serves thesefunctions, thus the saline bag 448 is for an alternate method of primingand rinseback. The optical fluid sensor 781 detects when the saline bagis empty, and permits automatic identification of the condition to thepatient, obviating the need for periodic checks of the saline bag 448.When air is sensed by the sensor 781, the clamp 779 is closed. Analternative to the use of a fluid sensor 781 is an in-line infusionfilter in the infusion set which obviates the need of a fluid sensor.

A clamp 444, an ultrasonic air bubble detector 446, a redundant pressuremonitor 500A, a pressure monitor 500B and an optional injection site(needle or needleless type) 456 are placed in the line 432. Blood pump458 pumps blood into line 462, via special pump section tubing (fromPharmed™ material or silicone) past injection site 460 and pressuremonitor 500C and (optional) expansion chamber 466 to the dialyzer 404.The blood is returned to the patient via line 470 to an air-separatingand pressure monitoring chamber 472 having an inlet tube 471 at the topor bottom, with the top preferred.

Referring in particular m FIGS. 13 and 27, the air-separating andpressure monitoring chamber 472 has a chamber 474, an upper and a lowerblood level sensors 476 and 478 respectively, and an optional injectionsite 480 (one or more). A third blood level sensor could be providedwith the chamber 472 for monitoring or monitoring or controlling theblood level. The chamber 474 is in air communication via line 482 to aconnection port 483 in a disinfection manifold unit 494, which isfurther connected to a line 491 having a pressure sensor 775, valve 777and then open to atmosphere. A restrictor may be needed in the line 491to control the rate of air flow in and out of the line 491. Because thefluid in the chamber 474 is normally under positive pressure duringdialysis, the level may be raised (when identified as being too low bythe level sensor 478) by opening valve 777 until the level is raised tothe level of sensor 476. The level may be lowered by stopping theocclusive blood pump 458, opening valve 777, and operating UF pump 242(FIG. 6) until the level is lowered and sensed by sensor 478. Analternative method would be to close venous clamp 490, open valve 777,and operate the blood pump 458 in reverse until air is sensed by sensor476. The bottom of the chamber 474 is connected to a line 484 having anultrasonic air bubble detector 486, a blood sensor 488 and a clamp 490and is connected to the venous line 492 which leads to the patient.

A pressure transducer isolator (a disc shaped unit) 493 (FIG. 36) isinstalled at the interface between the line 482 and the port 483. Theisolator 493 has a microporous membrane which allows no fluid to escapeout of the line 482 but which allows air to escape and enter the line491.

It is common in extracorporeal blood circuits to have a blood filterwhich filters the blood as well as eliminates air or gas bubbles. Thetypical application for these filters is in major surgical procedures.The blood flow rate for these surgical procedures range from 3 to 6liters per minute. The typical blood flow rate for hemodialysis is only200 to 600 milliliters per minute.

It is well known that air contact with blood often causes clotting. Thisis one of the draw backs of traditional bubble traps. Bubble traps alsorequire level sensors and a valving scheme and control system to allowthe collected air escape. By using a hydrophobic microporous membrane toallow the air to escape passively, less clotting occurs, less sensingand valving hardware is needed, and fewer set manipulations by thepatent or machine operator are needed. In addition, the unit is simplerto clean and sanitize. Thus, an alternative to the air separating andpressure monitoring chamber 472 is a cassette-type debubbler 1000, shownin FIGS. 15A-15D. FIG. 15A is an exploded view showing the front orblood side of the debubbler 1000, FIG. 15B is an exploded view showingthe rear or air side of the debubbler 1000. FIG. is a cross-sectionalview of the debubbler 1000 through the blood outlet 1020 in an assembledcondition, with the unit in a vertical orientation as it wouldpreferably be installed in the extracorporeal circuit 400 (FIG. 13).FIG. 15D is a perspective view of the debubbler 1000 partially brokenaway in section in the same plane as FIG. 15C. Also for this applicationthe debubbler 1000 is designed to be cleanable, sanitizable andreusable.

Referring to FIG. 15A, the debubbler 1000 has a front cover 1002, afluid circuit board 1004, two microporous membranes having a bloodcontact portion 1006 and a secondary air vent 1006A, a back cover 1008with pressure transducer opening 1016A and an over molded supportportion 1010 having a series of parallel support ridges 1024 separatedby adjacent parallel apertures 1115. The fluid circuit board 1004 has ablood chamber 1014 and an optional pressure transducer opening 1016disposed therein. A retaining ting 504 and pressure transducercomprising diaphragm 506 with metal disk 508 are mounted within theopening 1016 for measuring the blood pressure in the blood chamber 1014.The magnet, rod and strain gauge elements of the pressure transducer aredescribed in construction with FIG. 14A-C below.

A condensate outlet 1018, a blood inlet 1022 and a blood outlet 1020 areprovided at the bottom of the fluid circuit board 1004. An air port 1012is also provided at the bottom for conducting air passed through thefilter 1006A and 1006 out of circuit board 1004. Referring to FIG. 15B,which is a exploded view of the debubbler 1000 seen from the tear or airside, the fluid circuit board 1004 also has a condensate chamber 1032and hole 1038 covered by membrane 1006A, a membrane peripheral seal area1028 where the microporous membrane 1006 is sealed to the fluid circuitboard 1004, a raised rib 1026 and a channel 1030 for collectingcondensate. Condensate is passed out of the unit 1000 from condensateoutlet 1018.

It is well known that hydrophobic microporous membrane filters willallow air to escape a chamber while preventing aqueous liquids to escapethrough the membrane. This also works with blood. PTFE, also known asTEFLON™, microporous membrane filters have been used successfully formany years. However, if blood flow is deadheaded against a PTFEmicroporous membrane filter, in a short period of time the membrane willbecome coated with a biofilm that impedes air escapement. It is wellknown that PTFE attracts lipids and proteins. It is also well known thatif the blood flow is allowed to flow past the microporous membrane in atangential manner, the flow minimizes the build up of a biofilm andbetter maintaining air escape efficiency.

Prior an air venting blood filters for surgical use typically employ anessentially horizontal inlet port that passes blood tangentially acrossa horizontal hydrophobic membrane. The blood flow across and around andthen down through a blood clot filter and out. There are severalvariations to this theme. There are reports that claim the clot filterscause more clots than they eliminate from the flow stream. All thesesurgical units are designed for single use and are relatively expensive.For our hemodialysis application, no clot filters will be used.

Recently, two microporous membrane manufacturers, Pall and Millipore,have introduced PVDF (polyvinylidene fluoride) also known as KYNAR™membranes that have superior hydrophobic properties over PTFE and whichreportedly do not have the protein and lipid attraction that PTFE has.PVDF is the preferred material for the membranes 1006, 1006A of thecassette-debubbler 1000 of FIG. 15. PVDF has the following properties:sealability to the PVDF microporous membrane, blood compatibility,natural hydrophobia, moldability, heat sealability, translucency and canbe compliant under pressure. Polysulfone could also be used as analternate material with difficulty and with a trade off in properties.

To achieve tangential flow, our microporous membrane filter 1006 isinstalled in an essentially vertical orientation. The blood inlet port1022 is also vertical, as is the outlet 1020. The inlet port 1022 can befrom either the top, bottom or side. Our preferred embodiment is havingthe inlet 1022 enter from the bottom.

The covers 1002, 1008 are heat sealed to the ribs 1027, 1026 using aheat seal process. The fluid circuit board 1004 is fabricated preferablyby injection molding with ribs 1027, 1026 forming channels on both sidesof a central plane 1029 of material. Three holes are provided in thefluid circuit board. The hole 1016 is for the silicone diaphragmpressure transducer. The silicone diaphragm or membrane 506 is to becaptured and secured by welding a retaining ring 504 over the edge ofthe silicone to a mounting structure 1036 on the fluid circuit board1004.

The hole 1034 is covered with the microporous membrane 1006 and sealedaround the edges to the fluid circuit board 1004. This can beaccomplished several ways. The membrane 1006 can be placed in the partand heat sealed in place at membrane peripheral seal area 1028 or heldmechanically in place. The preferred embodiment insert molds themembrane in place. To insure even better seal integrity, the insertmolded membrane 1006 can be over molded with support member 1010.Coincident with the over molding would be the addition of suitablesupport ribbing 1024.

The membrane 1006 is placed over the hole 1034 from the back side of thefluid circuit board 1004 (FIG. 15B), the back side being the non-bloodcontact side. Placing the membrane 1006 from the back is necessarybecause the objective is to be able to eliminate all the air from thechamber 1014 on the blood side (FIG. 15A). If the periphery seal wasaccomplished from the blood side, then the seal area at the top of thechamber would be higher than the active membrane area, making total airelimination impossible. Total air removal is important for sanitizationpurposes.

Usually, insert molded filters are designed such that the direction offlow applies force perpendicular to the peripheral seal area and againstthe seal area. Because of the total air removal issue, the fluid flow inthis instance applies a peel force to the peripheral seal when themembrane is placed from the back. Integrity of the filter membrane 1006and seal is dependent on the membrane strength and the peel sealstrength. A second insert molding of an overseal around the periphery ofthe membrane 1006 is used to better secure the membrane 1006 andeliminate the possibility of the pressure exceeding the peel forcestrength. The membrane 1006 ends up sandwiched between two layers ofplastic. With the over molding 1010 of the seal, support members 1024are also added to further support the membrane 1006 against the flowpressure preventing distortion and possible rupture of the membrane1006. Alternately, this can also be accomplished mechanically. Themembrane filter 1006 material may or may not have a polymer screen meshincorporated into its structure to improve membrane strength.

Blood enters the blood side of the chamber 1014 through the inlet port1022. The flow is directed to the center of the chamber 1014 to gentlydisrupt the flow pattern and allow the previously entrained bubbles tocontact the microporous membrane 1006 and escape. To enhance contacttime with the microporous membrane 1006, the distance between the frontcover 1002 of the chamber 1014 and the microporous membrane 1006 ispreferrably 1/8 inch or less. For typical bubble traps the volume andgeometry of the chamber required is considerably larger. This isnecessary in order to slow the blood flow down and give the entrainedbubbles time to escape the viscous blood.

The back side of the fluid circuit board 1004 (FIG. 15B) manages the airthat passes through the microporous membrane 1006 and condensate formedduring sanitization. Air and condensate is allowed to flow intocondensate region 1030 and down and out the exit port 1018 to drain viasilicone tubing, a connector, a pinch valve and suitable internalmachine plumbing (not shown).

Air is let in or out through the air port 1012 at the bottom of thecassette via silicone tubing, a connector, a pinch valve and suitableinternal machine plumbing. Some condensate is also allowed to exit thecassette through port 1012. In the preferred embodiment of the cassette,the air will be directed through the hole 1038 back to the front of thefluid circuit board, down a channel 1040 (FIG. 15A) and out the bottomof the cassette at air port 1012. The hole 1038 is covered by amicroporous membrane 1006A. This membrane could be an extension to theoriginal membrane or a separate piece as shown. The second membrane1006A serves as a safety mechanism. Should the primary membrane 1006fail, the patient could suffer a potentially catastrophic loss of blood.With the secondary membrane 1006A, if the primary membrane 1006ruptured, the blood would be stopped by the second membrane. A blooddetection sensor (not shown) is provided to sense the presence of bloodon the back side of the cassette and the activate an alarm and stop themachine. The blood detection sensor is similar to the blood leakdetector 428 described above. Because the volume of space between thetwo membranes is sterile (ETO or radiation sterilization post assembly),the patient will not be at risk of infection should the primary membranerupture.

During sanitation, if condensate occurs on the air side of the membranes1006, it can be removed by allowing the condensate and air to exit thecassette from the bottom via port 1018 utilizing gravity. If condensateoccurs on the down stream side of filter 1006A it can be removed byallowing the condensate and air to exit via port 1012. Otherwise acondensate build-up could act as a shutoff valve and block all airpassage in or out.

Referring to FIG. 13 and FIG. 36, the disinfection manifold 494 includesdisinfection ports 495, 497 and 499. Port 495 is connected at the backside of the manifold 494 to disinfection line 496, which carriesdisinfection fluids (e.g., hot water) to the extracorporeal circuit 400.Ports 497 and 499 receive the connectors at the end of the venous andarterial lines 432 and 492, respectively after the dialysis session iscompleted. Ports 497 and 499 are connected to each other via valve V20(FIG. 6). Port 497 and port 495 are connected via a T fitting on theback side of the disinfection manifold 494. These connections provide apath for the flow of disinfection fluid (i.e., hot water or watertreated with disinfection chemicals) through the entire extracorporealcircuit 400, including the blood side of the membrane in the dialyzer404. The port 483 is not in fluid communication with the other ports495, 497, 499. When the dialysis session is completed, the patientreconnects the bubble trap line 482 from the port 483 to thedisinfection port 495. While the disinfection manifold 494 could beformed as a unitary housing, it may also simply be composed as an arrayof connectors having the fluid communication pathways described herein(or equivalents). Referring now also to FIG. 6 and 36, it will be seenthat lines 289A and 236A connect at the back side of the disinfectionmanifold 494 to ports 499, 497.

The back side of the disinfection manifold 494 is connected via returnlines 236A and 289A to valves V14, V20, check valve CV 11 and thermistor293 (FIG. 6). Lines 236A and 289A connect through the disinfectionmanifold to the arterial 432 and venous 492 lines, respectively, of theextracorporeal circuit, when the lines 432 and 492 are connected to theports 499, 497 of the disinfection manifold 494, as shown in FIG. 27.

The preferred design of the connection terminals for the lines 432 and492 is shown in FIG. 37A-C and 38A-D. A preferred design of the ports ofthe disinfection manifold 494 are shown in FIG. 39A-C. Referring to FIG.37A-C, an integral inner piece or male luer with luer lock 550 is shownin an end view in FIG. 37A, a cross-sectional view in FIG. 37B, and in aelevational view with a tube 552 in phantom in FIG. 37C. The male luer550 receives the end of a silicone tube 552 by insertion of the tubeover the cylindrical tubing port 554. A secondary silicone oversleevecould also be placed over the tube 552. The male luer 550 has a lockinghub 556 with threads 560 disposed on its inner surface. The connectorfurther includes a second elongate spout or tube portion 558 integralwith the wall 562 and tubing port 554. A pair of apertures 551 areprovided in the side walls of the locking hub 556 to allow air to ventout of the interior of the locking hub 556. At least one aperture isneeded on connectors with integral nonrotating locking hubs. Theaperture can be anywhere on the locking hub shoulder.

Referring to FIG. 37D, in operation, male luer 550 locks onto femaleluer 559 by virtue of threaded engagement of flange 561 of female luer559 with threads 560 of male luer 550 and rotational movement of lockinghub 556 relative to female luer 559. In FIG. 37D, an alternativeconstruction is shown in which the locking hub 556 is a separatespinning hub piece that snaps over a circumferential ridge 555. Airvents out of the hub 556 by virtue of the clearance 553 between thelocking hub and the integral tube 557.

The connection terminal further includes a separate outer piece 570,shown in FIGS. 38A-D. FIG. 38A is a perspective view of the outer piece570 prior to pushing the outer piece over the male luer 550 to securethe two pieces together. FIG. 38B is an end view of the outer piece 570.FIG. 38C is a sectional view of the outer piece. The generally elongatecylindrical outer piece 570 has a housing 572 with a recessed notchportion 574 on its outer surface, a series of axially disposed raisedridges 576 circumferentially disposed on the housing, with or withoutspaces 577 between the ridges 576. A slanted shoulder region 578 isdisposed adjacent to the end region 579 of the piece 570. The interiorregion of the piece 570 is dimensioned to provide compression on thetube 552 preferrably 360 degrees around the tube and male luer 550 whenthe outer piece 570 is pressed in a friction fit over the tube and luer550. The recesses 577 can be omitted with housing 572 smooth at thethickness of ridges 576.

Referring to FIG. 38A, the outer and inner pieces 570 and 550 aresecured together by inserting the outer piece 570 over the end of thetube 552 and firmly pressing the outer piece 570 onto the inner piece550 (see arrow, FIG. 38A) such that the interior region snuglycompresses the silicone tube 552, resulting in the construction shown inFIG. 38D. Alternatively, and referring to FIG. 38E, oversleeve 583comprising a short tubing segment can be installed over the end of thetube 552, and the interior surface 584 can have 3 or 4 longitudinal ribs581 projecting inwardly from the interior surface 584 that securely gripthe tube segment 583 and tube 552 when the second piece 570 is snuglyinserted over the male luer 550. Alternatively, the outer and innerpieces 570 and 550 could be formed as a single integral unit, withtubing port 554 extending rearwardly past the end of the cylindricalhousing 572 to allow insertion of the end of the tube 552 onto thetubing port 554. See FIGS. 38F-38G.

The connection terminal of FIG. 38D is applied to the ends of thearterial and venous lines 432 and 492. The terminals are inserted intothe preferred manifold port design, shown in FIGS. 39A-C. In FIG. 39A,the connection port 499 there illustrated is the same as the other ports497 and 493. The port 499 is shown in a elevational view in FIG. 39A,and end view in FIG. 39B, and in a sectional view in FIG. 39C. Theconnection terminal of FIG. 38D is installed in the connection port 499as shown in FIGS. 39D and 39E.

Referring to FIG. 39A, the port 499 consists of a housing 632 definingaxis 661 with a flange 634 for mounting the port 499 to the disinfectionmanifold 494 housing (or perhaps to the side of the machine if thedisinfection manifold is arranged as an array of ports). Screw threads636 are provided for accommodating a threaded nut for securing thehousing 632. Six apertures 638 are circumferentially spaced about thehousing 632 with steel bearings 637 placed therein. Upper and lowerprojection elements 640 lock the knob 641 in place when the knob 641 ispushed against the force of the biasing spring 643 in the direction ofthe flange 634 and rotated. The notch 642 retains a retaining ring 695for knob 641 in place. An elastomeric O-ring 650 is placed in theinterior 654 of the port 494. The tube end 644 of the port 644 includesan optical detector comprising a light generation unit 646 and a sensor648 with a lead going to CPU 610. Sensor 648 detects the presence of aconnection terminal within the port 499. The tube end 644 accommodates asilicone tube (such as line 289A) in the manner described below inconjunction with FIG. 24.

Referring to FIGS. 40A-40E, the knob 641 is shown isolated from the restof the port 499. Knob 641 is shown in a side elevational view in FIG.40A, with surface 699 oriented towards flange 634 and surface 645oriented towards the outside as shown in FIG. 39E. FIG. 40B is an endview of the knob. FIG. 40C is a sectional view of the knob along theline 40C--40C of FIG. 40B. FIG. 40D is an opposite end view of the knob,with recessed portions 653 fitting over projections 640 of FIG. 39A.FIG. 40E is a sectional view of the knob 641 along the line 40E--40E ofFIG. 40C. Races 657 accommodate the projections 640. The outer turn ofthe biasing spring 643 seats against the inner wall 655 of the knob. Thespring biases the knob 641 to an outer position. The knob 641 locks onto projections 640 when the knob 641 is pushed to an inner position suchthat the projections 640 pass into recessed portion 653, and the knob isturned such that projections are rotated into race regions 657.

Referring to FIGS. 39D and 39E, the connector assembly of FIG, 38D isshowed installed in the port 499. To establish the connection, the userinserts the connector 550, 570 into the port 654. To lock the connector550, 570 in place, the user pushes the knob 641 against spring 643 suchthat portion 647 is positioned over the bearings 637, pushing thebearings 637 radially inward into notch region 574 of the outer piece570. The shoulder 578 seats against the O-ring 650, with male luer 550projecting into the region 652 of the port 499 where it can be sensed bythe sensor 648. The knob 641 is rotated clockwise over the projection640 (FIG. 39B) into a locked position. The bearings 637 are securelypositioned within the notch 574 of the outer piece, preventing removalof the connection assembly 550/570.

When the connector assembly 550/570 of FIG. 38D is installed as shown inFIGS. 39D and 39E, it will be appreciated that complete disinfection ofthe interior and exterior surfaces locking hub 556 is accomplished whendisinfection fluids are circulated within the port 499. In particular,if the patient contaminates (as by touching) locking hub 556 or spout558 of the male luer 550 when disconnecting from the arterial or venouslines from the fistula needle, these surfaces of the male luer 550 aresubject to hot water disinfection when the connector 550, 570 isinstalled on the port 499 during the disinfection cycle. Moreover, byreason of the clamping engagement of the outer piece 570 onto the tube552 and seating of the shoulder region 578 of the outer piece 570against the O-ring 650, and the locking engagement of the outer piece570 to the port 499, fluids will not escape past the O-ring 650 into thechamber 654.

The pressure sensors 500A-C of FIG. 13 are of the same design, which isillustrated in detail in FIGS. 14A-14C. FIG. 14A is a cross-section viewof the sensor 500, FIG. 14B is a top plan view of the sensor 500 in anassembled condition, and FIG. 14C is a sectional view of the diaphragmdement 506. The sensor 5130 includes a housing 502 and a retaining ting504 which retains the diaphragm 506. The diaphragm 506 is placedopposite a wall 520. The diaphragm 506 is a preferably a circularresilient silicone membrane (or the equivalent) having an upper surface526 and a lower surface 524 in contact with fluid within the chamber 522of the sensor 500. A circumferential retaining rim 528 integral with theupper surface 526 of the diaphragm 506 retains a metal disk member 508on the upper surface 526 of the diaphragm. The magnetic metal member 508is placed into contact with a magnet 510 mounted to the distal portion514 of a rod 512. The metal member 508 may be coated to preventcorrosion or leaching of chemicals. It could aim be made from plasticimpregnated with metal. The metal must be magnetic. The rod 512 includesa lever member 516 connected to a strain gauge 518 that measures theback and forth movement of the rod due to the movement of the diaphragm506 caused by pressure variations in the chamber 522. If a ferromagnetis chosen for the magnet 510, the magnet 510 is in continuous contactwith the metal member 508. When the magnet 510 is an electromagnet, themagnet 510 would come into contact with the metal member 508 when themagnet is energized by an electric current.

The required magnetic force per unit area for the present application isabout 11.6 pounds per square inch. For a disc 508 with a diameter of0.441 inches, the preferred design, the required magnetic force is 1.77lbs. The ideal force is a little greater, about 2 pounds.

The pressure sensors 500A, 500B monitor the pressure in the arterialline 432. If for some reason the arterial fistula needle gasaccidentally positioned against the wall of the patient's blood vessel,the pressure will generally drop. The CPU 616 (FIG. 16) monitors thereadings of sensors 500A, 500B and, if the pressure drops, it promptsthe patient to move about to free up the needle or adjusts the bloodpump 458 to bring the pressure to acceptable limits.

The efficiency of a dialyzer in removing toxins is maximized if thedialysis time is made as short as possible. The faster clearance of urearequires a faster flow rate of the patient's blood. We achieve a fasterflow rate by taking advantage of a lower limit of pressure to bemonitored by pressure sensor 500B that is safe for conducting dialysis.This pressure limit would be set by the patient's physician. As long asthe pressure is above this limit, the pump rate of the blood pump 458 isgradually increased. If the pressure drops below the limit, the bloodpump is slowed or stopped if the pressure fails to rebound. When thepressure rebounds, the pump is speeded up. This feedback control of ablood pump 458 by pressure monitors in the arterial line will permit thesystem to generally shorten the dialysis time, to inform the patient ofthe expected time for dialysis, and to update the time based on anysignificant slowing or speeding of the blood pump 458. During thisprocess, the backup pressure sensor 500A provides data in case of amalfunction in sensor 500B. Ordinarily, the pressure sensors 500A and500B have the same readings. The pressure sensors 500A-C are calibratedagainst the reference sensor 410 in the dialysate circuit 402 asdescribed below in conjuction with the pressure test of theextracorporeal circuit.

The blood sensors 446 and 486 are of the same basic design as the bloodleak detector, but without the beam splitter and referencephotodetector. The sensors 446 and 486 serve two purposes: (1) to detectblood when blood is first introduced into the extracorporeal circuit400, thereby permitting calculation of the time elapsed during dialysis,and (2) permitting automatic rinse back control by automatically endingthe rinsing back of the blood when the light transmission levelsdetected by the sensors 486 and 446 rises to a threshold value. Asdialysate (or saline) is pumped through the dialyzer 404 duringrinseback, the blood concentration in the lines 432 and 492 diminishes.When the blood concentration has been diluted to a threshold level, asdetermined by the blood sensors 446, 486, rinseback is deemed to havebeen completed. Clamps 444, 490 close, the blood pump is stopped, theinput and output valves 414 and 416 for the dialyzer 404 close, andbypass valve 412 opens. During rinseback, the time and flow rate of theultrafiltration pump 242 and blood pump 458 must be coordinated toinsure equal pressure in the lines 432, 492. Generally, theultrafiltration pump 242 pumps at twice the pump rate of the blood pump458. This creates the pressure differential in the dialyzer 404 and asplit flow of blood/dialysate in the arterial and venous lines of theextracorporeal circuit 400. Further, by knowing the flow rate and thevolume of blood in the extracorporeal circuit 400, it is possible todetermine the time for rinseback and blood can be automatically rinsedback without monitoring the concentration of blood in the arterial andvenous lines. As another alternative, the blood may be rinsed back withsaline from a saline bag with blood concentration measured in the venousline. This technique is discussed in detail below.

Leakage from the various lines and hardware components of extracorporealcircuit module 28 out of the tubing or hardware components is indicatedby a leak path 430 (dotted lines). In use, the module 28 is placed abovethe other modules of the machine 22. A suitable drain and drain tube areprovided from the extracorporeal circuit module 28 to the bottom of thehousing of the entire machine 22, where such leakages may sensed by thefluid sensor in the catchment basin of FIG. 6. Alternatively, a bloodsensor and fluid leak detector may be installed in the base of theextracorporeal circuit module 28 for leakage detection in

The tubing (lines) used in the various modules 20, 24, 26, 28 ispreferably a silicone tubing, as silicone tubing is biocompatible,translucent, susceptible to disinfection by hot water, oxidationchemicals and other disinfecting chemicals, and has a long operationallife. Note, however, for the section of tubing used in the blood pump458 we prefer to use a tubing that has superior anti-spallingcharacteristics, such as the PharMed™ polyolefin-based thermoplasticelastomer tubing from Norton Chemical, or the equivalent.

Silicone tubes are inert to most bonding solvents, so a way of fasteningthe tubes to the hardware was invented. A preferred technique forconnecting the silicone tubes to the various hardware or rigidcomponents of the machine (such as the pumps, valves, thermistors,tanks, filters, etc.) is shown in FIGS. 24A and 24B. A generic siliconetube 900 is shown connected to an arbitrary piece of hardware 902 byinsertion of the free end of the tube 906 over an entry port 904 for thehardware 902. To keep the free end 906 securely installed on the port904, we use a short section of tubing 908 typically having the samediameter as the tube 900 and insert the segment 908 over the other end901 of the tube 900, spread the segment 908 apart with any suitableimplement such as a tubing expander, and the segment over the tube tothe end 906 until the segment 908 covers the port 904 and end 906, asshown. An alternative method of making the clamping connection is tofirst thread the segment 908 over the free end 906 of the tube 900,expand the segment 908 and end 906 of the tube with a tubing expander,and place the free end 906 and segment 908 over the port 904.

Different wall thicknesses and diameters of the segment 908 and tube 900may still be used. The segment 908 can be the same tubing as thesilicone tube 900. This construction gives good clamping results. Wehave found it particularly advantageous to have the segment 908installed relative to the port 904 such that the outside end 903 of thesegment 908 extends past the end 905 of the port, as shown in FIG. 24A.This construction creates a slight circumferential bulge 907 on theinside of the tube 900, preventing fluids from leaking around the edge905 of the port.

V. The User Interface and Control Module 25

Referring now to FIG. 16, the user interface and control module will nowbe described. The module 25 includes a display 600 which displaysmessages and information concerning the status of the system to thepatient. A touch screen 602 (or alternatively a keyboard) interfaceswith the patient and is provided for inputting commands or informationfrom the patient into a human interface (HI) board 608.

Indicators 604, including lights and audio indicators, and a speaker606, alert the patient to abnormal conditions in the machine 22, andprovide information as to the status of the modes of operation of themachine.

The module 25 includes a host central processing unit 610 connected viahigh speed digital data busses 611 and 613 to a driver board 612 and ananalog board 614. The central processing unit 610 has an associatedmemory (not shown) that stores the operating software for the machine 22and for other operational requirements, such as storing data from thesensors, and storing data input from the patients. Analog board 614contains analog to digital converters for converting incoming analogsignals from the passive sensors in the machine 22 into digital signals.The driver board 612 receives commands from the CPU 610 and sends thecommands to the valves, pumps, heaters, motors, and other activecomponents of the machines (represented by 620) to cause the componentsto change their status, e.g., commence or cease operation or changerate, as in the case of a pump, or open and close, as in the case of avalve. The signals from the passive components 622 of the system, forexample, the conductivity sensors, touch button readers, pressuretransducers, thermistors, provide their inputs to the analog boards 614and 618. The CPU 610 and driver board 612 together act its a controllerfor the active components.

Analog board 618 provides digital information on bus 617 to a safety CPU616. Safety CPU acts as watchdog of critical system sensors, andprovides enable signals to the driver 612 that allow certain drivercommands to issue to the active components 620 (such as enable signalsthe motor to move the spike in the chemical applicator 260 to open thebottle when the correct indicator has been read on the side of thebottle). Communications between the CPU 616 and host CPU 610 are passedon data bus 609. The safety CPU 616 activates if certain alarmconditions are present in the machine.

VI. System Operation

The operation of the constituent components of the machine 22 iscontrolled by a software program resident in the memory of the host CPU610. FIGS. 17-23 illustrate in flow diagrams the individual routines andsubroutines of the software (or, equivalently, operational sequences andmodes of the machine 22). These routines and subroutines, the inputs andoutputs to the CPU, and the operation of the other modules 24, 26 and 28of the machine 22 are described in detail in this section.

The condition or state of the various sensors, valves, pumps and othercomponents during the routines and subroutines of FIGS. 17-23 isillustrated in the tables of FIGS. 28-33. FIGS. 28 and 29 show thestates of the components of the water pretreatment module 24. FIGS. 30and 31 show the states of most of the components of the dialysatepreparation module 26, with the states of several of the components ofthe dialysate circuit 402 and the components of the extracorporealcircuit module 28 shown in FIGS. 32 and 33. In these tables, thereference numerals of the components are listed on the left-hand side ofthe table, and the modes of the machine from FIGS. 18-23 are placedacross the top of the tables. In FIGS. 34 and 35, the alarms for themachine 22 are listed on the left hand side of the tables and the modesof operation of the machine are placed across the top of the tables.Before describing the sequences and modes in detail, we describe belowthe system-in-progress and self-check routines that are performed whenentire machine 22 is turned on or when power is restored after atemporary power interruption.

Upon power on, the machine performs self-checks necessary to ensurecorrect operation. If there is an error in any portion of the machine,the user is notified, as by displaying messages on the display 600,illumination of indicator or warning lights 604, or other suitable meansconsistent with FDA/AAMI/IEC standards. An indicator light 604 for poweris preferably provided, allowing distinction between the absence ofpower and a system failure. It is preferred that the machine 22 be sexup with auxiliary equipment, such as a fax/modem for reporting theresults of the dialysis treatments to a central monitoring station, ablood pressure cuff, a scale for weighing the patient, and heparininfusion apparatus. The self check routines should determine the statusof these features as well.

After the self-checks have been performed, the unit 22 performs acycle-in-progress check to determine whether it was in mid-process(e.g., clean, disinfect, dialyze) when power was withdrawn. If thesystem was in mid-process and the power-off time was minimal, the systemwill continue the process.

If the disinfecting process was being performed, the CPU 610 can bepreprogrammed to either continue or display message for operator topress "Resume". Default is that it continues, showing status. Whencontinuing, the temperature of the system must be checked. Preferablythere is a method of determining, based upon time elapsed without powerand the current temperature of the device, whether the heat cycle is tobe merely continued, lengthened, or completely rerun with a possibleflush. The result must be that the disinfection cycle achieves therequired limits of bacterial presence.

If the tank 202 was being filled, the CPU determines, based upon timeelapsed without power, whether the existing water should be drained orwhether the fill should be continued from the existing level. Ifbacteriologically safe to continue from existing level, the systemcontinues filling, showing status. If not safe, the system drains andbegins filling again. Depending upon time elapsed, it may be necessaryto rerun the disinfect cycle.

If the dialysate was being mixed, the system determines, based upon thetime elapsed without power, whether the existing batch is "safe" frombacterial growth and precipitation. If not, the operator is to benotified that the batch must be discarded. Preferably, the system isuser programmable as to whether this is an audible as well as visualalarm. Default is audible as well as visual. If "safe", the mixingprocess continues, showing status.

If the extracorporeal circuit was being primed, the system determines,based upon the time elapsed without power, whether the existing prime is"safe" from bacterial growth and precipitation. If not, the operator isto be notified that the prime must be disregarded, and that an entirelynew batch of dialysate must be prepared. If "safe", the priming processcontinues.

If the clearance test process was being performed, the system notifiesuser that valid clearance test data could not be obtained (only thesophisticated user may be interested, but the treatment report given tothe center should indicate the lack of clearance test data). If a shortenough time period has elapsed the system will continue dialyzingagainst the blood side until a proper electrolytic concentration andtemperature are assured on the blood side. If too much time had elapsed,the system notifies the user that the prime must be disregarded, andthat an entirely new batch of dialysate must be prepared.

If the initiate dialysis process was being performed, the systemdetermining, based upon the time elapsed without power, whether theexisting prime is "safe" from bacterial growth and precipitation. Ifnot, the operator is notified that the prime must be disregarded, andthat an entirely new batch of dialysate must be prepared. If "safe", thesystem continues recirculating the dialysate and maintaining itstemperature.

If the dialyzing process was being performed, the system checks to seeif bloodlines are connected to the machine. If bloodlines are connectedto the machine, it determines time elapsed since removal of power. Ifsafe time for bacterial growth, it asks if it should begin a cleaningcycle or if the user wants to reconnect. The system should only allowpatient re-connection (and/or allows dialysate to be taken out ofbypass) when the dialysate is at the correct temperature andconductivity. If the temperature gradient no longer allows forseparation (if that method is used), it must account for this inreporting of therapy adequacy. If too much time elapsed for thedialysate to be "safe", the system asks to begin cleaning cycle. It maybe programmed to begin automatically, as long as bloodlines 432, 492 areconnected to the machine at 495, 497 (FIG. 13). If the bloodlines arenot connected to the machine, (i.e., probably connected to the patient),the system asks the patient if they wish to resume dialysis, rinse backblood, or merely disconnect. If resuming or rinsing back blood, itnotifies the user that they are to verify that safety clamps are putback in operating position (i.e. not opened manually). The system alsoverifies the temperature and conductivity of the dialysate. If thepatient is continuing treatment, the treatment continues from where itwas interrupted.

If the rinsing back blood process was being performed, the resumeprocedure is the same as the dialyzing process.

If the waiting for patient disconnection process was being performed,the system checks to see if the bloodlines are connected to the machine.If not, it asks the patient to disconnect. If so, the system asks tostart the cleaning cycle; but it could be programmed to start cleaningautomatically if the bloodlines are connected to the machine.

If the taking of blood pressure was being performed, the system beginsblood pressure measurement again. The system looks to see the timeelapsed since power was removed. The system may need to delay the numberof minutes before retaking the blood pressure, due to rebound in thepatient's body.

Referring now to FIGS. 16 and 17, after the system and in-progresschecks have been performed, the system enters an idle state 702. Anoverview of the sequences of operation of the machine represented byFIG. 17 is described here. In the idle state 702, the machine 22 waitsfor a user input to commence dialysis. The machine 22 monitors the timeelapsed since the last dialysis treatment. If the time since the lastdisinfection is greater than 48 hours, the machine enters a disinfectsequence 704. In the disinfect sequence 704, the entire machine isdisinfected with hot water of a temperature of greater than 80 degreesC. for a period of at least an hour. If the thermistors in the modules24, 26 and 28 report temperatures of greater than 80 degrees C. to theCPUs 610 and 616 for one hour, the machine initiates the preparedialysate sequence 706. After the dialysate has been prepared, themachine commences the initiate dialysis sequence 708. When the primingof the extracorporeal circuit has been completed, the machine enters adialyze sequence 710, where blood and dialysate are circulated tothrough the extracorporeal circuit and dialysate circuits 400, 402,respectively. When the ultrafiltration volume, KT/V parameter anddialysis time objectives have been met for the dialysis session, themachine commences the rinseback sequence 712, in which remaining bloodin the extracorporeal circuit 400 is returned back to the patient. Whenthis sequence has been completed, a clean and rinse sequence 714 isperformed. After the rinse has completed satisfactorily and waste fluidshave been flushed from the machine out the drain line, the machinereturns to the idle mode 702 and waits for a command or the scheduledtreatment time to occur and repeats the process.

It should be further noted that after a dialysis session has beencompleted, the arterial and venous lines, 432 and 492 (FIG. 13) areconnected to their respective ports 497, 499 of the disinfectionmanifold 494. This connection provides a pathway for reverse osmosiswater from the dialysate preparation module 26 to be introduced into theextracorporeal circuit 400, since the ports 497, 495 are connected tolines 289a and 236a (FIG. 6), linking the two modules together. Thisconnection is important for performance of a number of specificfunctions relating to the extracorporeal circuit as described later.

It should also so be noted that the disinfection temperature of the hotwater (80 degrees C.) and the time for the hot water circulationthroughout the machine 22 (1 hour) is not the only possible choice. Theachievement of high level disinfection of fluid circuitry with water isa function of the water temperature and the length of time of hot watercirculation. Hotter water will require less time for circulation andcooler water more time. In practice, a high level disinfectiontemperature will generally be determined or selected in advance andcontrolled by the operation of the water heater 228 in the machine andstrategically placed thermistors, and the circulation time controlled bya clock in the CPU of the control module 25 and the operation of thepumps and valves of the machine.

A. Disinfect Sequence 704

FIG. 18 is detailed flow diagram for the disinfect sequence 704. Duringthis sequence, the system decontaminates the dialysate preparation,water treatment, and extracorporeal dialysis modules, 26, 24, 28respectively, within a bacteriologically acceptable window prior to thenext treatment. Reference should be made to FIGS. 5, 6, 13 and 18 in thefollowing discussion.

At step 716, the system checks to see that the chemical loadingmechanism 260 is closed (i.e., the spike is in the lower position) andthat the drain outlet of the machine 22 is connected to a drain source.The valve 72 in the water treatment module 24 is switched to allow waterto enter the water filtration unit 84 (FIG. 5). Pressure sensor 98 ismonitored to see if water pressure is present at the inlet of thereverse osmosis filter 100. If the water pressure is below a specifiedlevel, an indicator or alarm is activated. The pressure drops across theprimary and secondary pre-films are calculated. The reverse osmosisfilter output valves 112, 108 and 80 are directed to drain water to thedrain line 71. The feed side of the reverie osmosis filter 100 isflushed with water.

At step 718, the reverse osmosis filter 100 is put in a mode to createfiltered water. The RO filter 100 valves are directed to bypass todrain. The filter unit 84 is then bypassed with bypass valve 83. Valve81 is toggled a number of times to prime the recirculation loop (lines110 and 116). The RO filter 100 valves are directed to bypass to drain.The system waits until the rejection conductivity exceeds a thresholdlevel.

At step 720, the RO filter 100 is placed in a generate product mode. TheRO filter 100 inlet and outlet conductivity and inlet pressure aremonitored and an alarm is sounded if necessary. The tank 202 is thenfilled with water, lines 206 and 209 (FIG. 6) are primed via valve 232.The UF pump 242 primes the dialyzer 404 via the valve 236 and lines 240,422. The valves in module 26 are then directed to prime thepyrogen/ultrafilter 234 (not through the dialyzer 404) back to the tank202. The UF pump 242 is then stopped, and the dialyzer 404 is primed inthe forward direction.

At step 724, the blood pump 458 is operated and the valves in the module26 are directed to transfer water from the tank 202 through thepyrogen/ultrafilter 234 to the dialyzer 404. The similarity of thethermistor readings of thermistors 408, 424, 216, 230 are compared andan alarm is activated if necessary.

At step 724, the RO filter 100 is directed to produce water. The valvesin modules 24 and 26 are directed to send filtered water to the tank202. The valves of module 26 are directed so that water from the tank202 goes through the pyrogen/ultrafilter 234 and back to the tank 202.The valves are directed so that water bypasses the dialyzer 404. Thesimilarity of the thermistor 408, 424, 216, 230 readings are comparedand an alarm is sounded if necessary.

At step 726, the CPU 610 begins accumulating time data for thethermistors. Valve V9 and check valve CV12 are primed using UF pump 242.The RO filter 100 is directed to produce water and fill the tank 202.The heater 228 is directed to heat water to 85 degrees C. The valves aredirected so that water bypasses the filter 234 and backfilters throughthe dialyzer 404 through valve 416. The blood pump 458 is turned on inthe reverse direction to recirculate water through the extracorporealcircuit 400. Heated water is sent through the chemical applicators 260and through valve CV9. When fluid sensor 288 senses a full tank 202, theRO filter 100 is directed to an idle mode. Water is directed through thefilter 234 and dialyzer 404. The UF pump 242 is run in reverse at 500ml/min with water sent through the chemical applicator nozzles 350 until3 liters of water remain in the UF tank 244. The RO filter is directedto produce water and fill the UF tank 244. The UF tank level sensor LUFis monitored and the UF tank is filled, with sensor 288 triggering,indicating the tank 244 is full. The RO filter is stopped. At the end ofthis mode, the tank 202 is filled with RO filtered water at atemperatures of at least 80 degrees C.

At steps 728, 730, 732, and 734, the heated water is circulatedthroughout the water treatment module, dialysate preparation module, andextracorporeal circuit module for at least an hour. The paths A, B, C,and D indicate that due to the particular valving and fluid line networkin the machine, the water cannot be passed through every fluid circuitat once, and that certain flow paths must be disinfected first beforeothers can be disinfected.

Step 736 indicates that in the event that any of the thermistors reporta temperature of less than 80 degrees C., the water is heated furtherand the cycle of steps 734, 728, 730 and 732 is repeated. As analternative, the water could be heated additionally above 80 degrees C.and the flow path affected, e.g. flow path "B", repeated a second time.As another alternative, an alarm could be activated or a chemicaldisinfection mode could be entered if the high level disinfection is notattained.

After the disinfection cycles have been performed, the machine enters adrain mode 738, where fluid is directed from the UF tank 244 through thedialysate module 26 to the drain line 107 in water treatment module 24.When the LUF sensor reads 0, mode 740 is entered, in which tank 202 isdrained.

The machine then enters a fill mode 742, in which the RO filter 100sends water to the tank 202. In rinse mode 744, water is directed fromthe tank 202 through the dialysate circuit 404 and back to the UF tank244. When the fluid sensor 288 at the top of tank 244 detects fluid, theRO filter 100 is set to an idle mode.

At step 748, water is directs through the sprayer 205 in the tank 202.Water is then directed from the UF tank 244 to the extracorporealcircuit 400 and back to the tank 202 until the UF tank 244 is empty.

At step 750, water is rinsed in the tank 202 via sprayer 205. At step752, water is directed from the tank 202 to drain. At step 754, RO wateris sent to the tank 202. At step 756, the blood pump 458 is run inreverse at 75 ml/min. Water is directed through the dialyzer 404 andback to the tank 202 through the chemical ports in the loading platform250. At step 758, water is drained from the tank 202. At step 760, thepump 212 speed is reduced to 300 ml/min. Water is directed from the tank202 through the dialyzer 404 and the extracorporeal circuit 400 and thento drain. The system waits until the tank 202 level sensor reads 1 andthe flow meter 241 reads less than 300 ml/min.

B. Prepare Dialysate Sequence 706

After the disinfection mode, the system enters a dialysate preparationsequence 706, described in detail in FIG. 19. At step 717, the processdescribed with step 742 above is performed. At step 719, the RO filter100 is placed in a produce water mode. The RO alarm monitoring ROconductivity in cell 106 is activated. RO filtered water is thendirected to the tank 202. Pump 212 is run at top speed in the forwarddirection. The tank 202 is placed in a recirculation and deaerationmode, in which water circulates out the tank 202 through degassing line209, through valves V9 and 220 and back to the tank via valve 232 andline 231 and valve V15. The temperature at thermistor 230 should read atemperature of 30 degrees C. The UF tank 244 is filled with 500 ml ofwater using the UF pump 242. The tank 202 is filled with reverse osmosiswater up to the level at which chemicals are added to the tank 202, andthen the RO filter 100 is turned off.

At step 721, the pressure sensors 500A-C in the extracorporeal circuitare calibrated against pressure sensor 410 in the dialysate circuit.Pressure variations in the dialysate circuit 402 are achieved by movingvolumes of fluid between the tank 202 and the ultrafiltration tank 244,with the introduction of fluid into the tank 202 causing an increase inpressure. Similarly, pressure variations in the extracorporeal circuit400 are achieve by introducing additional volumes of fluid into theextracorporeal circuit via disinfection manifold 494. This calibrationtest is advantageous in that it permits the use of disposable, off theshelf pressure transducers to be used in the extracorporeal circuit 400.It also permits high accuracy of the monitoring of the blood pressure inthe extracorporeal circuit 400 during dialysis. To accomplish this, thevalves are switched to direct dialysate-side fluid through the dialyzer404 and pressure sensor 410. The valves are switched to isolate the tank202 from the dialysate pathway. UF pump 242 is run in reverse to directfluid from the UF tank to the dialyzer 404 and the extracorporealcircuit and to pressurize the dialysate circuit 402 to 300 mm Hg. If thepressure sensors 500A-C in extracorporeal circuit 400 fail to pressurizeor the rate of decay exceeds a predetermined limit, an alarm isactivated, indicating a leakage in the extracorporeal circuit 400.Assuming no leakage, the pressure reading of sensor 410 is used tocalibrate the pressure sensors 500A-500C in the extracorporeal circuit400.

The UF pump 242 is then run in the forward direction, removing fluidfrom the dialysate circuit 402, and the pressures is stabilized at about10 mm Hg. A second calibration of the pressure sensors 500A-C is thendone, and gain and offset values for the sensors are determined. Analarm indicating a failure of the pressure sensors is activated. The UFpump is run in the forward direction until negative pressure isdeveloped, and the additional calibration of the pressure sensors isperformed. Additional negative pressure is generated and anothercalibration is performed. Then, UF pump 242 is run in reverse, thepressures are stabilized at 0 mm Hg. and the tank 202 is vented toatmosphere.

At step 723, a test the integrity of dialysate circuit andultrafiltration control system is performed. When the test is initiated,the level of water in the tank 202 is up the to level of the chemicalloading platform, the RO filter is in an idle mode and the arterial 444and venous 490 clamps of the extracorporeal circuit 400 are open. Thevalves of module 26 are switched to direct water away from the dialyzer404 and to isolate the tank 202. The fluid lines of the dialysatecircuit 402 are completely full. This fluid circuit is a closed system,with valves 414 and 416 closed with bypass valve 412 open. Theultrafiltration tank 244 contains some reverse osmosis Water. The UFpump 242 is operated in the reverse direction to pump water into line240 in the dialysate pathway. This increases the volume of water in theclosed system, causing an increase in pressure. Pressure sensor 410 inthe dialysate circuit 402 monitors the increase in pressure. Any failureor leakage in the system will be detected by the rate of decay in thepressure monitored by sensor 410, activating an alarm. The pressure inthe extracorporeal circuit 400 is also monitored and slowly reduced withthe blood pump 458.

At step 725, the ultrafiltration pump 242 is calibrated against the flowmeter 241. Fluid is directed from the tank 202 through the UF pump 242to the filter 234 and back to the tank 202. Valves V9 and 412 are pulsedto clear air from the lines of the dialysate circuit 402 The flow meterreadings are monitored as the speed of the UF pump 242 is varied. A bestfit calibration line from the readings of flow rate and UF pump speed iscalculated in the CPU 610

At step 727, a test of the integrity of the fibers in the dialyzer 404is performed to insure that the dialyzer 404 does not have any leaks. Weperform this test with air pressure, similar to the fashion in which theultrafilter/pyrogen filter 234 is tested. To perform this the clamp 490is closed and valve V14 is closed. Air is pumped by the blood pump 458from the ultrafiltration tank 244 into arterial be line 432 (viadisinfection manifold 494) up through the dialyzer 404 to displace anyfluid through valve 414 until the fluid is substantially removed fromthe lumen side of the dialyzer 404 The pressure sensor 500C in theextracorporeal cut 400 monitors the pressurization of the dialyzer 404and the pressure decay in the line 462. If the sensor 500C fails torecord an adequate pressure or the decay rate is too great, the dialyzer404 is deemed to have filed the test and the user to the need to replacethe dialyzer.

At step 729, the integrity of the pyrogen/ultrafilter 234 is tested.This test was described in detail above in the discussion of thedialysate preparation module 26.

At step 731, the extracorporeal circuit 400 is filled with water. The ROconductivity and pressure are monitored. The UF tank 244 is filled withapproximately 1 liter of water using UF pump 242. The RO filter 100 isplaced in an idle mode. RO water is directed through the dialyzer 404from the UF tank 244 back to the tank 202 using the blood pump 458.Then, water is back-filtered through valve 416 while venous clamp 490 ispuked to fill the air separating chamber 474 (FIG. 13). Valve V13 ispulsed to clear air from the arterial extracorporeal circuit line 432.When the UF tank 244 is empty, the clamps 444, 490 are closed and theblood pump 458 is closed.

At step 733, RO water is pumped from the tank 202 to the dialyzer 404.The dialyzer 404 is bypassed for a short period of time and then wateris backfiltered across the membrane of the dialyzer 404 into theextracorporeal it 400 and back to the tank 202 to prime theextracorporeal circuit 400. During these steps, the blood pump 458 isrun in reverse during bypass and then forward during backfiltration.

At step 735, the extracorporeal circuit 400 is flushed with freshreverse osmosis water to eliminated air and bubbles from the circuit.The automatic priming process may be implemented as a sequence of stepspre-, during, and post-dialysate preparation, depending on the mosteffective and efficient way to achieve priming and dialyzer clearancetest requirements A new extracorporeal circuit will be required when thedialyzer 404 is determined to have a leak or unacceptable performanceduring the clearance test, in which case replacement occurs after thebatch of dialysate has been prepared and the clearance test has beenrun, or, if the dialyzer clogs during treatment, in which casereplacement occurs mid-treatment, or when the dialyzer was determinedduring the previous treatment's clearance test to be adequate for thattreatment only and replacement should have occurred prior to thepreparation of the new batch of dialysate and prior to the new clearancetest.

During the prime mode 735, water is pumped through the dialyzer 404(with valves 412, 414 closed and valves 416, 232 and V15 open). Theextracorporeal circuit lines are put in a recirculation mode with V20closed. To shear any remaining bubbles from the fibers of the dialyzer404, pressure surges (or spikes) are in induced in the arterial line 432This is accomplished by opening and closing in rapid success the clamps490 and 444 and varying the flow direction of die blood pump 458.Pressure increased in the lines the clamps are closed and the blood pump458 continues to pump, and when the clamps are opened the release ofpressure within dialyzer 404 shears the bubbles from the fibers. Valve416 is also pulsed to cause backfiltration to shear bubbles from thefibers.

Priming is also assisted by periodic backfiltration of water across thedialyzer 404. The backfiltration of fluid across the dialyzer isaccompanied by the introduction of pressure pulses in the dialysatecircuit 402 The pressure pulses in the introduction of fluid across themembrane causes air bubbles to be sheared off the blood side of thedialyzer membrane. The air bubbles are then conducted from the bloodside of the dialyzer and out of the extracorporeal circuit 400. Thedialysate is pumped at a high flow rate through the dialysate circuit402, and a valve in the dialysate circuit is opened and closed tothereby introduce pressure pulses in the fluid. The backfiltration mayoccur in synchrony with the pressure pulses introduced in the dialysatecircuit 402

At step 737, the RO conductivity and pressure is monitored and thedialysate tank 202 is filled with RO water unless the level is above thelevel of the chemical loading platform 250. The UF tank 244 is drained.Water is pumped to the filter 234 and away from the dialyzer 404, withthe water heated by heater 228 to 37 degrees C. The tank return valveV18 is closed and water is directed from the tank 202 through valve 236into the UF tank 244 using the UF pump 242. The UP tank 244 is filled.The tank return valve V18 is opened.

At step 739, the RO conductivity and pressure are monitored and RO wateris sent to tank 202 until the proper level for addition of dialysatechemicals is reached. The bottle 270 containing powdered chemicals ispierced by the chemical applicator 260, and chemicals are purged fromthe bottles 270 by periodic short bursts of water from the nozzles 350in the applicators 260 (FIG. 12). The sprayer 285 in the loadingplatform 250 rinses the chemicals off of the shelf of the platform 250into the tank 202. As water is circulated through the tank and outletline 206, the conductivity 218 monitors the conductivity of thesolution. Additional water is added to the tank 202 if necessary. Theadditional dialysate chemicals in the second and third chemical bottlesare then released onto the platform 250 by operation of the chemicalapplicators 260. The liquid chemicals are added just before the fluidlevel reaches the level of the nozzle 352 in the applicator 260. Thetank 202 is then filled completely with water.

At step 741, the system enters a mix mode in which the dialysatechemicals are mixed in the tank 202. The chemicals are mixed in the tankusing the process previously described. During the mixing mode,conductivity sensor 218 monitors the conductivity of the dialysate inthe line 206 and reports the measurements to the CPU 610. A safeconcentration of chemicals is verified by conductivity measurements inconductivity sensor 218 and/or by sampling the dialysate in sampler 210.Preferably the dialysate is circulated from the tank outlet, through theconductivity sensor 218 and back into the top of the tank 202 viasprayer 205 during the mixing process. When the conductivity of thedialysate remains constant for a sufficient period of time, the solutionis deemed mixed. During the mixing process, the dialysate is not sentthrough the ultrafilter or dialyzer but rather it is circulated from thebottom of the tank out line 208 through valve V9 to valve 232 and backvia line 231 and valve V15 and sprayer 205.

At step 743, a conductivity test is performed with the purpose to verifythat conductivity cells 426 and 218 have the same readings. Dialysate ispumped from the tank 262 through the ultrafilter 234 and dialysatecircuit 402, through bypass valve 412 and back to the tank 202. An alarmis activated if the conductivity readings are not substantially thesame, indicating a failure in one of the conductivity cells. Also, thereadings of the thermistors 424 and 408 are compared, and an alarm isactivated if the readings of dialysate temperature are not substantiallythe same, indicating a failure of one of the thermistors.

At step 745, a dialyzer clearance test mode is entered. Prior toconducting dialysis, the integrity of the dialyzer 404 and the ureatransmission rate through the membrane of the dialyzer should bechecked. On average, extracorporeal circuits are reused from 12-15 timesbefore they must be discarded. In order to determine whether theextracorporeal circuit should be replaced, its clearance must be tested.We perform the clearance test after dialysate chemicals have been mixedin the tank 202, and with the ultrafiltration tank 244 filled withapproximately 4 liters of reverse osmosis water heated to a temperatureof 37 degrees C. The dialysate temperature is about 30 degrees C. Theextracorporeal circuit 400 is filled with reverse osmosis water.

The machine 22 tests the clearance of the dialyzer 404 by takingadvantage of several properties of the Na+ ion: the Na+ ion is about thesame size as the urea molecule that Na+ is the dominant cation in adialysate solution, and that Na+ is very conductive and able to bemonitored with precision with a conductivity monitor, such as the twononinvasive conductivity cells 218 and 426 in the dialysate preparationmodule 26. The Na+ ion is used as a substitute for urea. Theconductivity sensor 218 measures the conductivity of the dialysate goinginto the dialyzer 404, and conductivity sensor 426 measures theconductivity of the dialysate coming out of the dialyzer 404.

The blood pump 458 continuously pumps pure reverse osmosis water throughthe blood side of the dialyzer 404 (i.e., single pass). The water flowsfrom UF tank 244 through valve V13, through line 289 and 289A to theport 499 in the disinfection manifold 494 (FIG. 13) of theextracorporeal circuit module 28, then into the arterial line 432 andthrough the circuit 400 and dialyzer 404, out the venous line 492 toport 497 of the disinfection manifold 494, and back to the tank 202 vialine 236 valve V21 and inlet 203. Simultaneously, pump 212 pumps freshdialysate through heater 228 where it is heated to 37 degrees C. andpumped through the dialysate circuit 402 and back to the tank 202. Atthe end of the dialyzer clearance mode 745, about 500 ml of RO waterremains in UF tank 244 at a temperature of 37 degrees C.

The measurements of conductivity are sent to the CPU 610 of theinterface and control module 25. The difference in conductivity been thesensors 218 and 426 is a measure of the urea clearance of the dialyzer404. As shown in FIG. 26, the conductivity measured by conductivity cell426 drops when the process is initiated, but soon levels off. When theconductivity measured by cell 426 has leveled off, the clearance of thedial dialyzer 404 in units of ml of sodium cleared per minute can becalculated by the central processing unit 610. A minimum conductivitylevel 759 may be determined for the sensor 426, and if the sensor doesnot record a conductivity below this level at steady state, a clearancetest failure may be deemed to have occurred.

An alternative method of determining whether the dialyzer needs to bereplaced is to compare the clearance coefficient K for the dialyzer withthe value of K when the dialyzer was new. Let C_(in) =Conductivity oninlet side of dialyzer, measured by 218, C_(out) =Conductivity on outletside of dialyzer, measured by 426. Let K= (C_(in) -C_(out))/C_(in) ! Xflow rate ml/min.!. Let K_(out) =the initial measurement of theclearance coefficient with the dialyzer was new. Before every dialysissession, K_(i) is determined as set forth above. When K_(i) ≦0.9K_(out), the dialyzer is deemed to be in condition for replacement priorto next treatment.

As a redundant safety measure, the machine 22 performs the clearancetest twice before conducting dialysis. If the dialyzer 404 fails bothtimes, a replacement message is displayed at the user interface advisingthe user of the need to replace the extracorporeal circuit and dialyzer404 prior to the next dialysis. The CPU 610 records a failure of thedialyzer including the clearance value and the date at which the failureoccurred.

At step 747, a mix mode is entered for the purpose of bringing theextracorporeal circuit 400 and UF tank 244 fluids up to the correctconductivity. Dialysate is circulated through the UF tank 244 with thetemperature controlled to 30 degrees C. After a certain amount of time,the conductivity of the UF tank dialysate becomes stabilized, and analarm is activated if the conductivity is outside of an expected range.The valves are switched to direct dialysate out of the tank 202 thoughthe pyrogen/ultrafilter 214 through the dialyzer 404 and into theextracorporeal circuit by backfiltration. The extracorporeal circuitdialysate flow is directed through the disinfection manifold 494 back tothe tank 202 with the assistance of the blood pump 458. When theextracorporeal circuit dialysate outlet conductivity has matched theinlet conductivity, backfiltration is ceased and diffusion across thedialyzer is allowed to occur, with valve 416 open. The fluid level inthe tank 202 is lowered below valve V6 if necessary

C. Initiate Dialysis Sequence 708

The initial conditions for the initial dialysis sequence are thecirculation of dialysate through the extracorporeal circuit at a correctand stable conductivity and temperature and the arterial and venouslines of the extracorporeal circuit are connected to the disinfectionmanifold 494 with the blood pump running in the forward direction.

Referring to FIG. 20, patient assessment is made at step 860. Aninitiation screen is displayed on the display 600, and the patient isprompted to initiate dialysis. The display 600 displays a patientquestionnaire, seeking input from the patient, such as their currentpretreatment weight, standing blood pressure and sitting blood pressure,The weight and blood pressure of the patient is taken and the data isentered into the CPU 610. After the patient assessment steps have beenperformed the system verifies that the saline bag 448 in theextracorporeal circuit is connected.

The system can be preprogrammed to dialyzer to the following combinationof parameters:

target KT/V per treatment, where K is the urea clearance of the dialyzerin ml of blood totally cleared in urea per minute, T is the treatmenttime, and V is the volume of distribution which is approximately equalto the total body fluid volume of the patient. The details of thecorrelation calculation between sodium and urea are set forth in theHoward et al. patent, U.S. Pat. No. 5,110,477, which is incorporated byreference herein.

Minimum treatment time, regardless of whether the KT/V target wasreached in a shorter amount of time.

Prescribed blood flow rate, with limits on maximum arterial and venouspressures;

Dry weights with limits also preprogrammed as a maximum rate at whichfluid can be removed (weight is removed then calculated by subtractingdry weight from preassessment weight and adjusting the additional fluidinfused during prime, rinseback and at other times) or

Fluid to remove, for example, in an acute setting, a removal amount maybe required based upon infusion volumes rather than patient weight andthe system will not be able to automatically calculate fluid removalfrom weight minus dry weight!, thus necessitating the operator todirectly specify the amount of fluid to remove.

Additional prescription parameters will be set by the physician such as,particular dialyzer to be used, the arterial pressure limits, venouspressure limits, fluid removal rates, dialysis flow rate, temperature,heparin dosage, and so on.

At step 802, heparin access site preparation instructions are displayedon the screen 600. Heparin connection instructions from the patient'sprescription are displayed. After the patient connects the heparininjection apparatus to the injection site in the arterial line 432, theuser is prompted to input an OK.

At step 804, protective system tests are performed to insure safety ofthe dialysis process. The tests include: arterial and venous air bubbledetectors, arterial and venous pressure tests (high and low), dialysatetemperature and conductivity tests, and blood leak detection tests.

After these tests have performed, the system at step 806 checks to seeif the extracorporeal circuit is to be primed with saline or blood. Ifsaline is used to prime the extracorporeal circuit 400, the user isprompted to begin saline prime. The user spikes the saline bag and thesaline line is primed. The blood pump 458 circulates 500 ml of salinethough the arterial and venous lines of the extracorporeal circuit, withthe fluids emptied out of the venous line 492 into a suitable container.The blood pump 458 is then stopped and the clamps in the arterial andvenous lines are closed.

A priming fluid can also be pumped through the extracorporeal circuit,connecting the patient to said arterial and venous lines of theextracorporeal circuit, and pumping priming fluid from theextracorporeal circuit through the dialyzer to said dialysate circuit.Then, blood is pumped from the patient into the extracorporeal circuitto the dialyzer and returned to patient, thereby avoiding pumping ofpriming fluid into the patient. The priming fluid is pumped through thedialyzer by the UF pump in the forward direction and the priming fluidis returned to the ultrafiltration tank.

If blood is used to prime the extracorporeal circuit 400, the machine atstep 808 prompts the user to insert the arterial fistula, unclamp thearterial fistula line, prime the arterial fistula line with blood,reclamp the fistula line and attach the fistula to the connector at theend of the arterial line 432. The venous connection is then made insimilar form. If necessary, the user is prompted to connect line 482 tothe pressure port 493 in the disinfection manifold 494. Dialysate ispumped through the dialyzer 404 to the UF tank. The blood pump 458 isrun in the forward direction until a slightly negative pressure in thearterial and venous line is sensed. The extracorporeal circuit pressurealarms are enabled, the blood sensors are enabled and the arterial andvenous clamps are opened. If the blood sensors in the arterial andvenous lines do not detect the presence of blood within a predeterminedtime period, an alarm is activated. The level in chamber 471 is loweredwith the venous clamp. After a small volume of blood has been drawn, thearterial clamp 444 is closed. The UF pump 242 is stopped and the valveV13 into tank 244 is closed. The user is prompted to confirm bloodcirculation. The air bubble detectors art enabled and the arterial andvenous clamps are opened. The blood pump 458 ramps up to the prescribedblood flow rate.

D. Dialyze Sequence 710

Referring to FIG. 21, at step 820, the thermal boundary layer betweenold and new dialysate in the tank 202 is established in the tank 202. Inthe preferred embodiment, 1 to 2 liters of dialysate is heated to atemperature of 37 degrees C. and introduced into the top of the tank 202in a nonturbulent manner as described in detail above. The heater 228controls the dialysate temperature to the prescribed temperature.

The trans-membrane pressure at dialyzer 404 is adjusted to prevent anynet water or dialysate transport across the dialyzer 404. Measurementsof the blood pressure on the inlet and outlet on the blood side of thedialyzer 404 are made with the pressure sensors 500C and 775. (FIG. 13).The average pressure between these pressures is then computed. Thepressure in the dialysate circuit is measured at pressure sensor 410,and the pressure in the dialysate circuit is adjusted to match theaverage pressure in the blood side of the dialyzer 404. The adjustmentof pressure is accomplished by operating the UF pump 242 in either theforward or reverse direction to pump fluid into or out of theultrafiltration tank 244 into the dialysate circuit. By using a closedloop ultrafiltration system with a substantially noncompliant tank 202,the addition or substraction of fluid from the dialyzate circuit 402(including the tank 202) adjusts the pressure in the dialysate circuit.The tank 202 need not be full during this process. This pressureadjustment technique prevents any unintended fluid transport across thedialyzer when dialysis commences.

After the pressure has been adjusted across the dialyzer, the patient'sblood is dialyzed at mode 822. The dialysis sequence continues until thetreatment time is up or the patient requests end of treatment. As the UFtank 244 is filled with the predetermined ultrafiltration volume for thedialysis session, the measurement of the volume of water removed fromthe patient is made by the level sensor LUF. As the patient's bloodfills the extracorporeal circuit 28, the level of the air separating andpressure adjusting unit 472 may be adjusted. The blood detectors 446,486 detect presence of blood in the extracorporeal circuit. Once bloodflow has been achieved and venous and arterial pressures have beenstabilized, the system remains in dialysis sequence until the treatmentis complete or stopped by the user. The time of dialysis is measured andtime remaining for the session may be displayed to the patient.

During the dialysis process, the membrane of the dialyzer 404 in theextracorporeal circuit 400 may be periodically backflushed (step 874)with fresh dialysate to remove any buildup of blood materials on theblood side of the membrane. This procedure increases the efficiency ofthe dialyzer 404, avoids the buildup of blood products in the dialyzerand prolongs the life expectancy of the dialyzer 404. The blood productsbuilding up on the membrane are momentarily forced off the blood side ofthe membrane by the dialysate flowing into the extracorporeal circuit400, and then, when the back flushing ceases, incorporated into theblood flow, where they are carried out of the extracorporeal circuit 400and back to the patient.

To accomplish backflushing of the dialyzer, fresh dialysate is takenfrom the tank 202 and passed through valve V9 up through theultrafiltration pump 242, which is operational in the reverse direction.Dialysate is pumped out valve 236, through CV12, up line 223 and 226 tothe pyrogen/ultrafilter 234 and up to the dialysate circuit 402 and intothe dialyzer 404 with valve 414 open and valves 412 and 416 closed.During this time, the blood pump 458 is slowed. The bursts of dialysatethrough the dialyzer 404 preferably are between 15 and 30 seconds inlength. The backflushing can be periodic during dialysis, or may occurone time or not at all, depending on whether the membrane of thedialyzer is performing efficiently. After the backflushing is completed,the UF pump 242 is stopped, valves 414 and 416 are closed and bypassvalve 412 is opened, the blood pump 458 is ramped up to normal speed,the dialysate pump 212 is started again at the prescribed speed, valve412 is closed and valves 414 and 416 are opened, the UF pump speed isrecalculated and the UF pump is stated up again in the forward directionat the proper rate. The above-described technique differs from thatdescribed in the Eigendorf patent, U.S. Pat. No. 5,259,961. In the '961patent, flushing of dialysate through the dialyzer is described as forthe purpose of flushing and filling the extracorporeal circuit.

In alternative steps 826 and 828, it will be seen that other physiologicsolutions may be used to backflush the dialyzer by connecting the sourceof fluid to the dialyzer inlet line 418 and providing a suitable pumpingand valving arrangement. One such type of solution is a saline solution.A reinfusion of the saline bag(s) may be performed if necessary.

During the dialysis process, the CPUs 610, 616 in the control module 25for the machine continuously monitor the various sensors (temperature,pressure, conductivity, air, blood, flow rate, UF tank level, etc.) inthe various modules 24, 26 and 28. Any errors in the monitoring andcontrolling of the various systems is controlled by an exceptionhandling routine which would take appropriate action to recover theoperation or notify the user of abnormalities Additionally, prior totreatment, the patient's blood pressure is taken and the updated bloodpressures are logged in a treatment log. When the treatment is complete,the message is displayed to the user and if the user desires moretreatment the system continues to perform the dialysis. After thetreatment is complete, or error conditions exist which cannot berecovered, the dialysis is stopped and the system enters a rinsebacksequence (FIG. 22).

E. Rinseback Sequence 712

The rinseback sequence 712 is illustrated generally in FIG. 22. When thedialysis session has been completed, the touch screen 602 in the centralcontrol module 25 displays a prompt to the patient asking whether thepatient wishes to have the remaining blood in the extracorporeal circuitrinsed back to the patient. The blood pump 458 is also stopped. Otherinitial conditions are that the UF pump 242 is off, the blood pump 458is on at the prescribed speed and the dialyze alarms are still active.

At mode 832, when the command to continue is received, dialysate ispumped through the dialyzer 404 and the tank 202 is pressurized to equalthe starting pressure measured at pressure sensor 410. Bypass valve 412is opened and valves 414 and 416 are closed. The blood pump 458 isstopped. The arterial and venous line clamps are closed.

At step 838, the system determines whether a dialysate or a saline rinseis to be performed. If dialysate rinse is performed, the system enters amode 834. In this mode, the heater 228 is turned off, pump 212 isstopped, and the valves in the module 26 are switched to directdialysate from the tank 202 to the dialyzer 404 inlet line 414 via theUF pump 242. The arterial and venous clamps 242 are opened. The bloodpump 458 is pumped in reverse at one half the UF pump rate. The UF pump242 pumps dialysate from the dialysate circuit through the dialyzer 404into the extracorporeal unit 400, pumping blood in the extracorporealcircuit 400 in equal volumes out the arterial and venous lines 432, 492back to the patient.

The optical sensors 446 and 486 in the arterial and venous lines 432,492 sense the concentration of blood in the lines 432, 492 as the bloodis being pumped from the extracorporeal circuit back to the patient. Thesensors 446 and 486 issue signals to the CPU in the control module 25.The CPU 610 monitors the signals and when the signals indicate theconcentration of blood in the lines has reached a predeterminedthreshold level, the blood pump 458 is stopped, thereby preventingexcess fluids from being returned to the patient.

When the pressure in the extracorporeal circuit 400 is stabilized, thearterial and venous clamps 444 and 490 of the arterial and venous lines432 and 492, respectively, are closed. The A user disconnect message isdisplayed and the patient reconnects the ends of the arterial and venouslines 432, 492 to the ports 499, 497 respectively, of the disinfectionmanifold 494. The patient also removes line 482 from port 483 to port495. The sensors 648 (FIG. 39C) in the disinfection manifold confirmwhether the lines are reconnected to the disinfection manifold 494.

The user is prompted to install new chemical bottles 270 onto thechemical applicators 260. The readers for the machine-readableidentifiers (such as touch buttons) on the bottle send bottleinformation to the CPU 610, which then alerts the user if the wrongbottle is installed. A message is then displayed to the user to connectthe water inlet and drain outlet of the machine to water inlet and drainlines (if not already so connected).

The user is then prompted to take chloramine samples from the sampleremoval ports in the water pretreatment module 20, and, if necessary,change the filter unit 40. After the user has inputted an "O.K" responsethat the chloramine test was passed, the rinseback mode is ended and themachine enters a clean and rinse mode.

If saline rinse is performed (mode 836), the heater 228 is turned off,the dialysate pump 212 is turned off, and a message is displayed tounclamp the arterial fistula and unclamp the saline line. The arterialair bubble detector is disabled. The blood pump 458 is run in theforward direction, pumping saline though the arterial line 432 and bloodand saline out venous line 492. The dialysate valves are directed awayfrom the filter 234 back to the tank 202. When the blood concentrationsensed by venous blood sensor 486 has reached a predetermined limit, theblood pump 458 is stopped, the pressure in the extracorporeal circuitare stabilized and the arterial and venous clamps are closed. The useris prompted to disconnect from the machine and the process continues thesame as for the dialysate rinse mode 834 above;

F. Clean and Rinse Sequence 714

The clean and rinse mode 714 is illustrated in FIG. 23. The machine nextmakes two passes through the steps 850-866 in FIG. 23. At drain A modeand step 850, the dialysate preparation tank 202 and UF tank 244 aredrained from the machine 22. Step 852 and 854 are the same as steps 742and 760 of FIG. 18, respectively, which were described earlier. At step856, the chemical ports in the loading platform 250 are flushed withwater. Steps 858 and 860 are the same as steps 756 and 744 of FIG. 18,respectively. The dialyzer 404 is then cleaned on-line in step 862.Steps 864 and 866 are the same as steps 748 and 750, described earlier.At step 868, the tank 202 is drained. The waste water is pumped outdrain fine 71 to drain output 51. After the clean and rinse mode of FIG.23 has been completed, the machine enters an idle mode and waits for thenext disinfection session to begin.

Our preferred technique for on-line, in situ dialyzer cleaning is to useautomatic hot water agitation of the blood and dialysate sides of thedialyzer membrane, followed by flushing of the dialyzer. No chemicalsare used. The blood circuit is further not subjected to airbornebacteria. The hot water agitation involves heating RO water (orphysiologic dialysate) with heater 228 to a temperature of between 37°C. to 85° C., introducing the heated water into the extracorporealcircuit via the disinfection manifold 494 and introducing pressurepulses in the extracorporeal circuit and dialyzer in the mannerdescribed above in connection with the dialyzer prime mode 735. Wefurther back flush RO water across the dialyzer from the dialysate sideto the blood side of the membrane with pressure pulses introduced in thedialysate circuit 402. The particulate matter, blood products and othermaterial which maybe adhered to the fibers in the dialyzer 404 arethereby removed from the surface of the fibers. By periodically flushingthe extracorporeal circuit with RO water and returning the fluid to thedrain during this process, the life expectancy of the dialyzer 404 issubstantially prolonged.

In particular, backflushing of the dialyzer 404 is accomplished byclamping valve 416 and opening valve V14 to drain. The blood pump 458 isstarted in a reverse direction at approximately 1/2 the rate of the UFpump 242 using the dialysate which provides a physiologic solution tokeep the blood products from clotting and forming more difficultsubstances to remove. The flow rate of the UF 242 and blood 458 pumps islimited by the maximum pressure at pressure transducer 410. The systemwill adjust the flow rate until either flow meter 241 reaches the presetmaximum flow rate, approximately 600 ml/min, or pressure transducer 410reaches the preset maximum flow rate. The flow rate measurement by flowmeter 241 can be stored by the central processing unit 610 and can becorrelated to the mount of fiber blockage in the system, i.e. the lowerthe initial flow rate, the greater the amount of blockage. If the flowrate does not reach a specified level of approximately 500 ml/min afterthe time allotted for backflushing, then the dialyzer can be identifiedas too blocked for usage by the central processing unit 610. The userwill then be alerted at the beginning of the next treatment that theextracorporeal circuit needs to be replaced before dialysis cancontinue.

Systematic forward and reverse flowing of the fluid in theextracorporeal circuit is accomplished by driving the blood pump 458 ina forward or reverse direction with the valves V14, 414, 416 closed andV20 open. This isolates the extracorporeal circuit 400 from the rest ofthe dialysis system and allows the fluid to be recirculated to scrub theresidual blood products out of the extracorporeal circuit. This forwardand reverse flow is continued for a preset time. At the end of thecycle, the fluid in the extracorporeal circuit 400 with the removedblood products is set to drain by opening V14, and backflushing thedialyzer as outlined above. This procedure can be repeated as many timesas desired.

VII. Auxiliary Functions of Machine 22

Preferably, the machine 22 has the capacity for automatic communicationof a treatment report to a central station or other entity monitoringthe patient's hemodialysis. This would normally be accomplished byincluding in the machine 22 a fax modem connected to a phone line thatis programmed to automatically fax a report of the hemodialysistreatment to the center. The treatment reports would include suchinformation as the patient's name, address and phone number, the dateand time of the report, the pretreatment weight, blood pressure, pulseand temperature, a dialysate code, conductivity measurements andclearance, heparin information, and the results periodic measurementsduring dialysis such as blood flow rate dialysate flow rate, arterialpressure, venous pressure, blood pressure, pulse, UF rate, total UPvolume and additional comments. Additional information which may beincluded in the treatment reports would be the occurrence of incidentssuch as when blood flow was stopped, at what time, when it was resumed,and any alarms that occurred. Additional information would include thetime the treatment was ended, the total dialysis time and the calculatedKT/V for the treatment. Finally, treatment reports could include thepost-treatment weight, post-treatment blood pressure, and answers topost-treatment assessment questions. Weekly treatment summaries, innumeric and graphical form, of the fluid removed. KT/V and bloodpressure would also be provided. The interface and control module 25would be provided with internal data retention and storage capacity(such as a hard disk drive) for storing such information (such as arandom access memory) until the data is later sent to a center.Equipment for local print-out for the treatment report is a furtheraccessory for the machine 22.

Preferably, the user interface and control module 25 for the dialysismachine 22 includes a software diagnostic routine which can be accessedfrom the user interface to check the various sensors in the unit 22 andto manipulate its activity. Ideally, the diagnostic murine will be ableto be accessed remotely by a modem such that service entity for themachine 22 can check the sensors, failure codes and other diagnostics inthe machine 22 remotely. Since the various modules 24, 26, and 28 of theunit 22 are modular, failures or servicing of the various modules in arelatively easy by replacing or swapping modules 24, 26 or 28.

From the foregoing description it will be appreciated that the inventivetechniques, flowpath and system components and subcomponents may be usedto provide hemofiltration and hemodiafiltration. Hemofiltration withpre-dilution is accomplished as follows. The output of the dialysatetank 202 will be directed as before through the dialysate filter(pyrogen/ultrafilter) 234. However, the output of the dialysate filer234 will be directed to a second depyrogenation filter 404A, the outputof which will be directed via T connector 404T into the extracorporealblood circuit 400 upstream of the blood inlet of the dialyzer 404.Dialysate line 418 is blocked off as shown. See FIG. 41. The closedvolume principle which allows the control of ultrafiltration in normaldialysis will also apply here such that any solution directed into theblood circuit 400 will be pulled back into the dialysate tank 202through the dialyzer outlet line. The ultrafiltration pump 242 may stillbe used to remove excess fluid.

For hemofiltration with post-dilution, the technique is the same as forhemofiltration with pre-dilution, but the output of the seconddepyrogenation filter 404A will be directed into the blood circuit 400following the blood outlet of the dialyzer 404 at T connector 404T. SeeFIG. 42.

For hemodiafiltration with post-dilution, the technique is the same asfor hemodiafiltration with pre-dilution, except that the output of thesecond depyrogenation filter 404A is directed via T connector 404A tothe blood circuit 400 downstream of the outlet of the dialyzer 404. SeeFIG. 43. A valve 414' and penstaltic pump 404P are placed in dialysateline L. Line 418 is opera via valve 414.

For hemodiafiltration with mid-dilution, in this implementation there isno second depyrogenation filter. Instead, the ultrafiltration pump 242is used to backflush ultrapure dialysate into the dialyzer 404 and thento remove this excess fluid. See FIG. 43.

A further additional aspect of the invention is that the use of the tank202 (which may be the same size or smaller) and the same chemical mixingapproach described herein, but to prepare a more concentrated batch ofdialysate which can be proportioned with the reverse osmosis outputwater during the dialysis treatment. This would be particularly usefulin longer treatments. The same size tank or a or a smaller tank 202maybe used. However, rather than mixing up a fully dilute batch ofdialysate, a concentrated batch of dialysate is prepared (using the samechemical addition principles as described in conjunction with thediscussion of the dialysate preparation module 26). This batch may thenbe proportioned with reverse osmosis product water during the dialysissession to achieve longer treatments without enlarging the size of thetank required. The incoming reverse osmosis water will be heated, andthere is a means for insuring that the concentrated dialysate solutionand the incoming reverse osmosis water are thoroughly mixed. Theincoming reverse osmosis water can be heated such as by the use oftemperature controlled mixing valve in the water pretreatment module 20.The means for insuring that the concentrated dialysate and the incomingreverse osmosis water are thoroughly mixed can be achieved by monitoringthe conductivity of the solution as the concentrated dialysate is takenout of the tank 202 past through conductivity sensor 218 and returned tothe top of the tank in conjunction with the mixing principles above.

VIII. Conclusion

From the forgoing detailed description, it will be apparent to a personof ordinary skill in the art that many variations and modifications ofthe preferred and alternative embodiments of the invention may be made,without departure from the true spirit and scope of the invention. Theterm "module", as used herein and in the claims, is intended to bebroadly interpreted as encompassing a component or group of componentsthat perform a specified function, such as treat water or prepare adialysate solution, whether or not such component or group of componentsis physically encased within a housing physically apart from othercomponents. Obviously, the selection of components that comprises a"module" is a matter of design choice. For example, the dialysatecircuit 402 is shown as part of the dialysate preparation module 26, butcould just as easily been made part of the extracorporeal circuit module28, with suitable connectors in the lines leading to and from thedialysate side of the dialyzer. The true spirit and scope of theinvention is defined by the appended claims, to be interpreted in lightof the forgoing specification.

Further, the term "purified water" used herein means water in whichimpurities have been removed. The technical definition of "purifiedwater", such as found in the United States Pharmacopoeia, is notintended.

We claim:
 1. In a dialysis machine, a method of conducting a clearancetest of a dialyzer and determining the need for replacement of saiddialyzer, the dialyzer having a blood side and a dialysate side,comprising the steps of:approximating the urea clearance of a dialyzerin a new condition by circulating reverse osmosis water on through saidblood side of said dialyzer and circulating a dialysate solution throughsaid dialysate side of said dialyzer, measuring conductivity of saiddialysate solution before and after said dialysate solution hascirculated through said dialysate side of said dialyzer, and determininga clearance coefficient K_(init) of the dialyzer from said measurementsof conductivity; storing in a memory for said dialysis machine the valueof K_(init) ; repeating the step of approximating the urea clearance ofsaid dialyzer after a dialysis session has been conducted by saiddialysis machine with said dialyzer by circulating reverse osmosis waterthrough said blood side of said dialyzer and circulating a seconddialysate solution through said dialysate side of said dialyzer,measuring conductivity of said second dialysate solution before andafter said second dialysate solution has circulated through saiddialysate side of said dialyzer, and determining a new clearancecoefficient K_(i) of the dialyzer from said measurements ofconductivity; storing in said memory of said dialysis machine the valueof K_(i) ; comparing K_(init) with K_(i) ; and responsively prompting auser of said dialysis machine to replace said dialyzer if K_(i)<K_(init) by a predetermined threshold amount.
 2. The method of claim 1,wherein said reverse osmosis water is circulated in a single passthrough said blood side of said dialyzer.